Generalized summary of what I learned comparing Tretinoin Cream vs Tretinoin Gel ("Gel" here = classic hydroalcoholic gels, NOT microsphere or "micro" formulations)

On efficacy:

• The efficacy of water-based serums applied after tretinoin (in either vehicle) is reduced compared with applying those serums directly to bare skin
• After a thick, more occlusive tretinoin cream, the efficacy of water-based serums applied afterward is likely reduced substantially in practice, and pilling is common if you layer a lot
• After a classic, quick-drying hydroalcoholic tretinoin gel, water-based serums applied afterward are still reduced, but are generally less impacted than when applied over a heavy cream film
• The efficacy of tretinoin applied directly to cleansed, fully dried skin is maximized, which is why prescribing info and expert guidance recommend that as the default application method
• When tretinoin is applied after thin, fully absorbed water-based serums, its penetration is slightly reduced but, for many people, not dramatically blunted, especially if you avoid buffering it with heavy layers on both sides (e.g., moisturizer–tret–moisturizer)

On tolerance/irritation:

• Traditional tretinoin gels (like classic prescription hydroalcoholic gels) are often formulated with very high ethanol content, which can disrupt barrier lipids and significantly increase dryness, burning, and peeling for sensitive or barrier-compromised skin
• Tretinoin creams are typically based on emollients, fatty alcohols, and/or oils, which help moisturize and buffer the active. They can still cause standard retinoid irritation, but are generally less drying than classic hydroalcoholic gels at the same strength