Myth: You Need to Apply Tretinoin Every Night

For those new or experienced with retinoids, you may have questions about the frequency of application or concerns about losing progress if you miss a night.  Research suggests that you don’t need to apply retinoids every night to reap their full benefits. The long-term effects of retinoids, particularly tretinoin, are largely driven by their ability to regulate gene transcription, which leads to lasting structural changes in the skin, rather than the more transient effects mediated by the molecule's influence on biochemistry outside the nucleus where the genes reside. 

How Retinoids Work: Genomic vs. Non-Genomic Effects

Retinoids like tretinoin work by binding to receptors in cells that influence gene activity in the nucleus, influencing processes such as keratinocyte growth and maturation, collagen production, and epidermal turnover. This is a slow-moving biological process— it takes 8-12 weeks to see improvement and may take 6 months for full effect (Wolverton). Unlike treatments that work through rapid, temporary biochemical interactions, the genomic effects of retinoids persist even when application is reduced, explaining why missing a night (or several) does not erase progress.

What the Research Says About Frequency

Long-term studies confirm that tretinoin leads to sustained collagen production, reduction in solar elastosis, and overall skin strengthening, even with less frequent application over extended periods. Research shows that when tretinoin application was reduced to three times per week or even once weekly, improvements in epidermal thickness, texture, and inflammation markers were still maintained. (Bhawan et al., 1996; Ellis et al., 1990; Bhawan et al., 1998).

The Practical Takeaway

Given that retinoids work at the genetic level, their effects accumulate over time. Unlike ingredients that work primarily through direct exfoliation (like AHAs and BHAs), retinoids initiate cellular changes that persist even if you skip a night or two.  Reducing application frequency to even a few times per week can sustain skin improvements, which is particularly useful for those who struggle with irritation or dryness.

In practical terms:

• New users: Start with 2-3 nights per week and increase frequency as tolerated.

• Long-term users: Daily use may accelerate results, but long-term benefits remain even with reduced frequency.

• Sensitive skin types: Using tretinoin 3-4 nights per week is sufficient for continued improvement while minimizing irritation.

  
  

Important Caveat

One thing worth noting is that while these studies show sustained skin improvements with tretinoin, they do not fully control for potential confounding variables like increased sunscreen use or other lifestyle changes that could have impacted the observations made. The Ellis et al. (1990) study even included providing sunscreen to patients as part of the intervention (although without a strict protocol monitoring), so it’s possible that lifestyle changes contributed to the observed benefits.

However, Kligman et al. (1993) investigated the effects of tretinoin on non-sun-exposed protected skin of elderly individuals. Participants applied tretinoin to the inner thigh (a consistently covered area) for 9 months, with the opposite thigh as a control. The results showed improved structure of both the epidermis and dermis, supporting the idea that tretinoin has structural benefits independent of mitigating the effects of sun exposure (Kligman et al., 1993).

Conclusion

The belief that tretinoin must be used every single night to be effective is not supported by research. The genomic effects of retinoids persist, leading to sustained skin remodeling and repair, even when application frequency is reduced to a few times per week. For many, this means less irritation, more manageable routines, and equally impressive long-term results.

Dr. Ryan M. Trowbridge, MD, MS, MA

Harvard-Trained Board-Certified Dermatologist and DermMythBuster

P.S. Have you come across any new or conflicting research on this topic? Please share—I’d love to explore it further with you!

Would you like to try tretinoin? You can obtain an online consultation from Dr. Trowbridge at Bridge Dermatology if you currently reside in California, Connecticut, Illinois, or Nebraska.

Citations

• Bhawan, J. (1998). Short‐ and long‐term histologic effects of topical tretinoin on photodamaged skin. International Journal of Dermatology, 37(4), 286–292. https://doi.org/10.1046/j.1365-4362.1998.00433.x

• Bhawan, J., Olsen, E., Lufrano, L., Thorne, E., Schwab, B., & Gilchrest, B. (1996). Histologic evaluation of the long term effects of tretinoin on photodamaged skin.. Journal of dermatological science, 11 3, 177-82 . https://doi.org/10.1016/0923-1811(95)00432-7.

• Ellis, C., Weiss, J., Hamilton, T., Headington, J., Zelickson, A., & Voorhees, J. (1990). Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin.. Journal of the American Academy of Dermatology, 23 4 Pt 1, 629-37 . https://doi.org/10.1016/0190-9622(90)70265-J.

• Kligman, A., Dogadkina, D., & Lavker, R. (1993). Effects of topical tretinoin on non-sun-exposed protected skin of the elderly. Journal of the American Academy of Dermatology, 29(1), 25-33. https://doi.org/10.1016/0190-9622(93)70147-L

• Wolverton, Stephen, E. and Jashin J. Wu. Comprehensive Dermatologic Drug Therapy. Available from: Elsevier eBooks+, (4th Edition). Elsevier - OHCE, 2020.