One of the most common and distressing post-operative complication is post-operative nausea and vomiting (PONV). Though PONV can occur after all surgeries but it occurs more frequently among middle ear surgeries, gynecological, obstetric, ocular and breast. Ramosetron a newer 5 HT3 receptor antagonist and dexamethasone, a well known steroid both have its own anti PONV effect, but to determine their combination of therapeutic and side effects we took up this study. This randomized prospective double blinded study was conducted in our Institute. Sixty patients of ASA 1 and 2 were randomized to two groups – Group R (n=30) to receive ramosetron 0.3mg; Group R+D (n=30) to receive Ramosetron 0.3mg + Dexamethasone 8mg. Standard General Anaesthesia protocol was followed. Study drugs were administered at the time of induction. PONV was studied for period of 24hrs. Severity was assessed using PONV Score. The adverse effects were also studied. The incidence of PONV is high in ramosetron alone (R) group, compared to combination (R+D)group, where none of the patients subjected to this group showed either nausea or vomiting (0%) or any other adverse effects. Hence, we concluded that, combination of dexamethasone 8mg with ramosetron 0.3mg can be effectively employed at the time of induction to prevent PONV in patients undergoing ENT surgeries. Both ramosetron and dexamethasone are cost effective and safe for prevention of PONV.