Purpose: To compare the efficacy of ondansetron-dexamethasone combination with ondansetron alone for prevention of postoperative nausea and vomiting (PONV). Methods: This double blind, randomized, prospective, Placebo controlled study was carried out in 120 patients, aged 20-60 yr, American Society of Anesthesiologists-I and II physical status posted for exploratory laparotomy for various clinical conditions under general anaesthesia The patients were divided into three groups of 40 each. Patients in each group received either 4ml Normal Saline or injection Ondansetron 4mg(2ml) + 2ml Normal Saline or injection Ondansetron 4 mg (2 ml) + injection Dexamethasone 8mg( 2 ml), one of the three regimes for prevention of PONV before induction. Nausea and vomiting were looked from 0 min upto 24 hours. Retching and vomiting were grouped together under common term ' emetic episodes '. Results: Though ondansetron was effective in controlling postoperative nausea, the ondansetron plus dexamethasone combination was more effective overall. Though ondansetron was effective in reducing postoperative emetic episodes, the combination of ondansetron plus dexamethasone was more effective.The requirement for rescue antiemetic was less in ondansetron group and least in ondansetron plus dexamethasone group. There was no significant difference between pain intensity and sedation between these groups at any time. Only adverse effect reported was headache in ondansetron and ondansetron plus dexamethasone groups. Conclusion: Ondansetron plus dexamethasone combination is more effective in reducing incidence of PONV without causing any major side effects. Throughout the study, ondansetron plus dexamethasone combination was superior to ondansetron alone in all respects pointing towards the potentiating effect of dexamethasone.