One hundred twenty patients undergoing rehabilitation after ACL reconstruction who reported acute pain were randomized to receive either 65% nitrous oxide (n = 60) or 100% oxygen (n = 60). The primary outcome of interest was pain score measured during rehabilitation training. Secondary outcomes included sedation level, range of motion, vital signs, satisfaction of participants and physicians, acceptance (willingness to use the gas again), and side effects. Outcomes were assessed at baseline, 5 minutes into the procedure, and 5 minutes after the procedure. Overall, the results of the study revealed that nitrous oxide significantly reduced pain scores (P < 0.001) and improved sedation, satisfaction, and acceptance compared to placebo, with only mild and reversible side effects. These findings suggest nitrous oxide is a safe and effective analgesic for acute procedural pain during ACL rehabilitation.