Purpose: We performed this study to test the hypothesis that nitrous oxide produces clinically significant bowel distention during laparoscopic abdominal surgery. Materials and Methods: Laparoscopic kidney donors were randomized into 2 groups. Group 1 received N2O and oxygen inhalation through anesthesia, and group 2 received a mixture of air and oxygen. All patients received the same preanesthetic and anesthetic medications. The surgeon was blinded to the use of N2O. The surgeon was given the option to discontinue N2O use (if it was used) if he/she thought that the bowel distention was increasing surgical risk. Postoperative data were collected on bowel symptoms, pain and recovery. Results: A total of 28 patients were enrolled in the study, 12 of whom received N2O (group 1) and 16 who did not receive N2O (group 2). Mild to moderate bowel distention was reported by the surgeons in 6 patients (50%) in group 1 and 1 patient only in group 2 (6%, p = 0.007). Severe bowel distention was encountered in 4 patients, 3 of whom received N2O (25% of group 1). Nausea and vomiting on postoperative day 1 was reported by 50% of patients in group 1 and 25% of group 2. There was no difference in the pain scores between the 2 groups. No intraoperative or postoperative complications were encountered. Conclusions: The use of N2O anesthetic causes bowel distention in 50% of abdominal laparoscopic donor nephrectomy operations. The distention was severe enough to interfere with the progress of surgery in 25% of cases and the use of N2O had to be discontinued. © 2007 American Urological Association.