To compare the efficacy of low dose fentanyl infusion and 24% oral sucrose in providing optimal pain relief during laser for retinopathy of prematurity (ROP), we enrolled fifty-eight spontaneously breathing preterm infants undergoing laser. The preterm infants were randomized to either fentanyl infusion (1 mcg/kg/hr) or 24% oral sucrose (2 ml). We evaluated and compared the proportion of time spent crying during the procedure, salivary cortisol before and after the procedure, premature infant pain profile- revised (PIPP-R) scores during the procedure, apnoea during and after the procedure, need for mechanical ventilation, and feed intolerance and urinary retention 24 h after the procedure between the two groups. We found that the proportion of time spent crying during the procedure was significantly less in the fentanyl group [62.5% (50.7-74.2) vs 73.8% (55.6-83.4); P = 0.02]. Average PIPP-R score during the procedure was significantly less in the fentanyl group [7.2 vs 9.0; (mean difference of – 1.8; P = 0.01)]. There was no difference in other outcomes between the two groups.Conclusion: During laser for ROP, low dose fentanyl infusion was found to be efficacious in reducing pain as compared with 24% sucrose.What is Known:• Preterm infants undergoing laser photocoagulation for ROP suffer significant amount of pain.• Standard of care for pain relief in infants undergoing laser therapy in developed countries is general anesthesia (GA) or combination of sedation, analgesia, and paralysis (SAP).What is New:• During laser photocoagulation for ROP, fentanyl infusion at low dose (1 mcg/kg/hr) is efficacious in reducing pain as compared to 24% oral sucrose.