BACKGROUND: The enhanced recovery after surgery concept, which was introduced 20 years ago, is based on a multimodal approach to improve the functional rehabilitation of patients after surgery. OBJECTIVE: This study aimed to validate an enhanced recovery after surgery protocol in gynecologic surgery for both benign and malignant diseases (endometrial cancer and advanced ovarian cancer) and to measure the adherence to the enhanced recovery after surgery protocol items in a randomized trial setting. STUDY DESIGN: In this trial (NCT03347409), we randomly assigned patients to undergo standard perioperative care or enhanced recovery after surgery protocol. The primary outcome is a shorter length of stay in favor of the enhanced recovery after surgery protocol. Secondary outcomes include measurement of adherence to the enhanced recovery after surgery protocol items: comparison of postoperative pain, vomiting, and nausea; anesthesiologic and surgical complications up to 30 days after surgery; rate of readmissions; the time to event in hours for bowel movements, flatus, drinking, hunger, eating, and walking; and the quality of recovery using a validated questionnaire (QoR-15). Finally, we explored the length of stay in the prespecified subgroups at randomization, based on the type of surgical access and gynecologic disease. RESULTS: A total of 168 women were available for analysis: 85 women (50.6%) were assigned to the standard perioperative care group, and 83 women (49.4%) were assigned to the enhanced recovery after surgery protocol group. The 2 groups were similar for age, body mass index, comorbidities, anesthesiological risk, smoking habits, surgical access, and complexity of surgical procedures. Seventy-two patients (42.9%) underwent surgery for benign disease, 48 (28.6%) for endometrial cancer, and 48 (28.6%) for ovarian cancer. Women in the enhanced recovery after surgery protocol group had a shorter length of stay (median: 2 [interquartile range, 2e3] vs 4 [interquartile range, 4e7] days; P<.001). A decreased rate of postoperative complications was noted for the enhanced recovery after surgery protocol group, as well as an earlier time to occur for all the events. Mean adherence to protocol items was 84.8% (95% confidence interval, 79.7e89.8), and we registered a better satisfaction in the enhanced recovery after surgery protocol group. The shortening of the length of stay was confirmed also in the prespecified subgroup analysis. CONCLUSION: Application of the enhanced recovery after surgery protocol in gynecologic surgery translated to a shorter length of stay regardless of surgical access and type of gynecologic disease. Adherence to the enhanced recovery after surgery protocol items in the setting of a randomized trial was high.