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To evaluate the possible effect of two leading soft contact lens care products on corneal sensitivity, relative comfort, and superficial corneal staining in adapted disposable soft contact lens wearers.Eight disposable soft contact lens wearers equally divided between habitual users of OPTI-FREE Express Lasting Comfort No Rub formula (Alcon Laboratories, Fort Worth, TX) and ReNu MultiPlus (Bausch & Lomb, Rochester, NY) were enrolled in this crossover study. The habitual lens care product was designated the first crossover period. Patients completed a visual analog scale rating of midday and end-of-day comfort, underwent slitlamp examination for staining, and had corneal sensitivity measured by Cochet-Bonnet esthesiometry before and after being switched to the alternative lens care product. The lens care product used was masked from the investigator.Patients habitually using OPTI-FREE Express reported higher comfort ratings than did patients using ReNu MultiPlus. On crossover, patients who initially used ReNu MultiPlus experienced similar comfort when using OPTI-FREE Express, but OPTI-FREE Express users experienced a substantial decrease in comfort when switched to ReNu MultiPlus. Esthesiometry showed significant differences in average sensitivity in favor of OPTI-FREE Express (P=0.0041). Statistical trends supported observed increases in corneal sensitivity when switching to OPTI-FREE Express and decreased corneal sensitivity when switching to ReNu MultiPlus. ReNu MultiPlus was also associated with slightly more corneal staining.ReNu MultiPlus, a biguanide-based contact lens care product, was associated with decreased comfort during midday and end-of-day periods. ReNu MultiPlus was also associated with significant reduction in relative corneal sensitivity compared to Polyquad-based OPTI-FREE Express. Disturbance to normal corneal sensitivity may play a role in contact lens–related dry eye and discomfort. Further investigation is warranted.