Importance: Optimal postoperative pain management is challenging. Virtual reality (VR) provides immersive, 3-dimensional experiences that may improve pain control and reduce reliance on pharmacologic pain management. Objective: To evaluate use of VR on postoperative pain management after head and neck surgery. Design, Setting, and Participants: This prospective, pilot randomized clinical trial was conducted at Oregon Health & Science University from July 2020 to October 2021 and included patients hospitalized after major head and neck surgery. Interventions: Similar 15-minute interactive gaming experiences (Angry Birds) using an Oculus Quest VR headset (VR intervention) or a handheld smartphone device (control). Main Outcomes and Measures: The primary outcome was postintervention pain reduction. Pain scores were obtained preintervention, immediately after intervention, and then hourly for 4 hours. Secondary outcomes included changes in opioid use, measured as milligram morphine equivalents (MMEs), and patient experiences with their intervention using 5-point Likert scales. Results: Of the 30 patients randomized for inclusion, the final population included 14 patients in the VR cohort and 15 patients in the control cohort; the majority of patients were male (26 of 29 [90%]), and the mean (SD) age was 58.3 (13.8) years. After outlier removal, there were clinically meaningful reductions in postintervention pain among patients in the VR group immediately after intervention (mean difference, -1.42; 95% CI, -2.15 to -0.70; d = 1.50), at 1 hour (mean difference, -0.86; 95% CI, -1.90 to 0.14; d = 0.67), 2 hours (mean difference, -1.07; 95% CI, -2.30 to 0.14; d = 0.69), and 3 hours (mean difference, -1.36; 95% CI, -2.80 to 0.13; d = 0.71) compared with patients in the control group. Patients in the VR group also demonstrated reductions in 4-hour postintervention opioid use compared with 4-hour preintervention opioid use (mean difference, -9.10 MME; 95% CI, -15.00 to -1.27 MME; d = 0.90) and 8-hour postintervention opioid use compared with 8-hour preintervention opioid use (mean difference, -14.00 MME; 95% CI, -25.60 to -2.40 MME; d = 0.94). There were no meaningful differences in subjective patient experiences with their respective interventions. Conclusions and Relevance: In this randomized clinical trial, VR reduced pain scores and opioid use compared with a control intervention. Virtual reality may be a useful adjunct for postoperative pain management after head and neck surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04464304.