One hundred and twenty-eight patients scheduled for an arthroscopic rotator cuff repair surgery were randomized to receive ramosetron (n=42), ondansetron (n=43), or placebo (n=43) for the prevention of post-operative nausea and vomiting (PONV). Outcomes of interest included the incidences of nausea, vomiting, headache, dizziness, and drowsiness, severity of nausea on a Visual Analog Scale (VAS), the use of rescue anti-emetics, incidence of a complete response (no additional post-operative nausea and vomiting, no rescue anti-emetic use), pain on a Visual Analog Scale (VAS), and the use of rescue pain killers. Outcomes were assessed up to 48 hours post-operation. The incidence and severity of nausea were statistically significantly lower in the ramosetron group compared to the control group 6-24 hours post-operation (p<0.05 for both). The use of rescue anti-emetics was statistically significantly lower in the ramosetron group compared to the control group (p<0.05). A higher proportion of patients in the ramosetron and ondansetron groups reported a complete treatment response compared to the control group at 6-24 hours post-operation (p<0.05 for both). Pain scores were statistically significantly lower in the ondansetron group compared to the ramosetron and control groups at 0-6 hours post-operation (p<0.05 for both). Lastly, the incidence of headaches was statistically significantly lower the control group compared to the ramosetron and ondansetron groups at 0-6 hours post-operation (p<0.05 for both).