BACKGROUND Postoperative nausea and vomiting (PONV) is a common distressing experience in patients following laparoscopic surgeries. This study was aimed at comparing the efficacies of Ondansetron-Dexamethasone combination with each drug alone as a prophylaxis against PONV in patients after elective laparoscopic cholecystectomy done under general anaesthesia. METHODS Hundred and fifty ASA I and II patients, aged 23 to 65 yrs, were enrolled in this prospective, randomized, double-blind trial to receive one of three treatment regimens: 4 mg Ondansetron (Group O), 8 mg Dexamethasone (Group D) or 4 mg Ondansetron plus 8 mg Dexamethasone (Group OD) (n=50 for each). A standardized balanced general anaesthetic technique was employed. Any episode of PONV and need for rescue antiemetic were assessed at six, 12 and 24 hrs post operation. Complete response was defined as no PONV in 24 hrs and need for rescue antiemetic was considered as failure of prophylaxis. Pain scores, time to first analgesia demand, amount of Meperidine consumption, adverse event(s) and duration of hospital stay were recorded. RESULTS Complete response occurred in 66.7, 66.0 and 89.4% in Groups O, D and OD respectively. Rescue antiemetics were required in 29.2, 31.9 and 8.5% of patients in Groups O, D, and OD respectively. Significantly high incidence of vomiting and failure of prophylaxis (19.1%) occurred in group D during the fi rst six hrs (P=0.023 versus O & 0.008 versus OD). More frequent antiemetic rescue was required in group O at 6 to 24 hr interval as compared to group OD (P=0.032). CONCLUSIONS Combination of Ondansetron and Dexamethasone is better than each drug alone in preventing PONV after laparoscopic cholecystectomy. Dexamethasone alone is significantly less effective in preventing early vomiting compared to its combination with Ondansetron; whereas Ondansetron alone is less effective against late PONV as compared with combination therapy.