Post-operative shoulder and subcostal pain are common after laparoscopic gynecologic surgery, often attributed to residual intraperitoneal carbon dioxide. This study aimed to evaluate whether active gas aspiration via a peritoneal drain reduces post-operative pain compared to standard manual gas evacuation. We conducted a single-center, randomized, single-blind, phase III clinical trial at the Oscar Lambret Cancer Center (France) from January 2022 to November 2023. Women aged ≥18 years undergoing laparoscopic or robot-assisted gynecologic surgery were randomized 1:1 to receive either manual gas evacuation (control group) or active carbon dioxide aspiration using a subcostal drain connected to vacuum (experimental group). All patients underwent pulmonary recruitment maneuvers. The primary endpoint was the incidence of clinically significant shoulder/subcostal pain (Numeric Rating Scale [NRS] ≥3) within 24 hours post-operatively. Secondary endpoints included pain intensity over the first post-operative week, analgesic use, and adverse events. A total of 166 patients scheduled to undergo laparoscopy (82 control, 84 experimental) were enrolled in the trial. At 6 hours and 24 hours post-operatively, the proportion of patients experiencing NRS ≥3 shoulder/subcostal pain did not significantly differ between groups (6 hours: 5/82, 6.1%, vs 2/84, 2.4%; 24 hours: 8/70, 11.4%, in both arms). Maximum overall pain during the first 24 hours was also comparable (NRS ≥3: 42/82, 51.2%, vs 47/84, 56.0%, p = .54). Analgesic consumption, pain at day 30, and adverse event rates were not significantly different. No complications were attributed to the aspiration technique. In this randomized trial, active gas aspiration via a peritoneal drain did not significantly reduce post-operative shoulder or subcostal pain compared to standard manual gas evacuation in gynecologic laparoscopy. Given the low incidence of significant pain and the lack of added benefit, routine use of active aspiration drains is not supported in this surgical context.