Abstract Purpose: This is a randomized controlled study aiming to evaluate the safety and efficacy of two different concentrations of topical nalbuphine hydrochloride, when used to relieve pain in the first days following photorefractive keratectomy (PRK). Methods: This is a prospective double blinded randomized clinical trial that included 189 patients who had PRK for correction of low and moderate refractive errors. Patients were randomly assigned to three groups according to the eye drops given to relieve pain in the first three postoperative days; the first group received topical nalbuphine with a concentration of 2 mg/ml (Group A = 64 patients), the second group received topical nalbuphine in a concentration of 1 mg/ml (Group B = 69 patients) and the third group received topical artificial tears only (Group C = 56 patients).The patients were asked to rate their pain daily using a numeric rating scale and to record the number of drops instillation times/day. The time needed for complete epithelial healing, best-corrected visual acuity (BCVA) and spherical equivalent after three months were recorded in each group. Results: In the first three days, there was a statistically significant difference in pain score among the three groups with lower values in the two topical nalbuphine groups when compared with the control group receiving artificial tears. Moreover, the higher concentration group showed significantly lower pain score and less number of drops used /day in comparison with the lower concentration group.There were no statistically significant differences in epithelial healing time, BCVA and spherical equivalent after three months among the three groups. Conclusion: The use of topical nalbuphine is effective in relieving pain in the first few days following PRK and this pain relief is not associated with any compromise regarding epithelial healing nor refractive outcome. The pain control with 2 mg/ml concentration is significantly higher than that with 1 mg/ml concentration of nalbuphine. Trial registration numberISRCTN21394752 https://doi.org/10.1186/ISRCTN21394752 The trial is retrospectively registered in ISRCTN registry at March 08, 2021. Keywords: Nalbuphine; Opioids; Pain control; Photorefractive keratectomy.