Chemotherapy has brought wonders to human race but also has got many adverse reactions. Out of which nausea and vomiting rank among top three adverse drug reactions. The desire to control chemotherapy induced nausea and vomiting (CINV) is strong that patients postpone or even refuse the treatment. Ondansetron and Granisetron are the most common drugs used for treatment of CINV. Hence this study is carried out to compare the efficacy and safety of these two drugs. Methods: This is a prospective observational study conducted in oncology department, KR Hospital, Mysuru. 150 participants who satisfied the inclusion criteria were enrolled for the study. Among them, 50 were given Ondansetron, 50 of them were given Granisetron and rest were given to Palonosetron for prevention of CINV. A well-designed data collection form was prepared to collect the data. Efficacy of antiemetics was assessed using NCI-CTC grading score. Result: The study showed that 20% experienced CINV while giving Granisetron plus Dexamethasone, 42% experienced CINV while giving Ondansetron plus Dexamethasone, 30% experienced CINV while giving Palonosetron plus Dexamethasone which indicates that Granisetron along with Dexamethasone is slightly better than the other. Conclusion: Though Granisetron regimen is found to be more effective, the choice of drug depends on the cost