The purpose of the study was to investigate the effect of upper limb massage on relieving pain among infants undergoing venipuncture in Hong Kong. This study was a crossover, double-blind, randomized controlled trial. Eighty infants at the neonatal intensive care unit were randomly assigned to 2 groups in different order to receive interventions. The massage first group (N = 40) received 2-minute massage before venipuncture on the first occasion then received usual care (control) on the second occasion, and vice versa in the massage second group (N = 40). The infants' behavior and physiological responses were recorded on two occasions: (1) right after the intervention and (2) during the first 30 seconds of venipuncture procedure. The mean pain scores (Premature Infant Pain Profile) were significantly lower in infants who received massage (massage first: 6.0 [standard deviation = 3.3]; massage second: 7.30 [standard deviation = 4.4]) versus control (massage first: 12.0 [standard deviation = 4.3]; massage second: 12.7 [standard deviation = 3.1]). The crude and adjusted generalized estimating equations model showed that the infants had significantly lower pain score when receiving massage as compared to receiving the control treatment, and there were no significant time and carryover effects: −6.03 (95% confidence interval: −7.67 to −4.38),p< .001 and −5.96 (95% confidence interval: −7.56 to −4.36),p< .001, respectively. Upper limb massage may be effective in decreasing infants' venipuncture pain perception.