Ankle sprains occur frequently among young and active people, accounting for almost 2 million injuries per year. Previous reports suggest that acupressure therapy for acute ankle sprains may shorten the recovery time. To evaluate whether acupressure therapy can improve ankle sprain recovery compared with standard RICE (rest, ice, compression, and elevation) treatment. A randomized controlled trial was conducted. The study protocol was registered in the Chinese Clinical Trial Registry with the study registration number: ChiCTR-TRC-14004794. Department of Traditional Chinese Medicine Orthopedics, PLA No.60 Center Hospital, Dali, China, and Department of Orthopedics, Xixi Hospital of Hangzhou, Hangzhou China, between June 2014 and January 2016. A total of 68 patients with acute ankle sprains were assessed for study eligibility, and a total of 62 patients were included in the present study. All patients with ankle sprains seen by the Orthopedics Department within 48 hours since the time of injury were identified. Consenting patients were randomized to either (1) standard treatment (ST group), (2) standard treatment + acupressure (AP group), or (3) standard treatment + mock acupressure (mock AP group). Outcomes of interest included a volumetric measurement of the foot, ankle, and lower leg), range of ankle movement, and visual analog pain scores. The American Orthopedic Foot and Ankle Score) and SF12v2 scores were used to assess quality of life. Among the 62 randomized patients, the mean (95% confidence interval [CI]) volumetric measurement of the foot, ankle, and lower leg in the AP group decreased from 185.24 (95% CI 142.80-227.67) to 62.14 (95% CI 44.03-80.25) after 3 sessions of acupressure treatment. This was a statistically significant difference (P < .01) compared with the means of ST group (119.00; 95% CI 89.14-148.86) and mock AP group (118.18; 95% CI 83.99-152.37). After the first treatment, the mean range of ankle movement, visual analog pain scores, and American Orthopedic Foot and Ankle Scores of the AP group were 31.67 (95% CI 27.78-35.55), 3.33 (95% CI 2.97-3.70), and 55.86 (95% CI 50.03-61.69), respectively. These scores were statistically better (P < .01) than the mean of the ST and mock AP group scores. In addition, the mean SF12v2 scores of AP group at 4 and 8 weeks were 109.95 (95% CI 107.29-112.62) and 119.67 (95% CI 119.27-120.05), respectively. These scores were also significantly greater than those of the ST group and mock AP groups (P < .01). Acupressure therapy may improve recovery after acute ankle sprain injury, yielding shortened time of disability and improved quality of life. I.