ABSTRACT Purpose: To determine whether codeine plus acetaminophen after photorefractive keratectomy (PRK) have beneficial effects on sleep quality, activity levels, and food intake, beyond their effect of pain relief. Methods: We enrolled 40 patients (80 eyes) in this randomized, double-blind, paired-eye, placebo-controlled, add-on trial. Each eye was treated 2 weeks apart, and the patients were randomly allocated to receive either the placebo or the intervention (30 mg codeine and 500 mg acetaminophen) (4 times a day for 4 days). Outcomes were sleep quality, daily activity level, and food intake within 24-72 h post-photorefractive keratectomy, as measured by the McGill Pain Questionnaire. Results: Sleep quality and daily activity level were inversely associated with pain scores within the first 48 h post-photorefractive keratectomy. During the intervention, patients were significantly more likely to score their sleep quality as good at 24 h (relative risk=2.5; 95% confidence interval 1.48-4.21, p<0.001) and 48 h compared to during placebo (relative risk=1.37; 95% confidence interval: 1.03-1.84, p=0.023). The probability of reporting good daily activity level at 24 and 72 hours post-photorefractive keratectomy was three times higher when patients received the intervention compared to the placebo (relative risk=3.0; 95% confidence interval: 1.49-6.15, p=0.006 and relative risk=1.31; 95% confidence interval: 1.02-1.67, p=0.021, respectively). No difference was observed in food intake. Conclusion: The oral combination of codeine and acetaminophen significantly improves sleep quality and daily activity level within the first 24-72 h post-photorefractive keratectomy compared to a placebo.