Background: Prevention of chemotherapy induced nausea and vomiting (CINV) is an essential part of cancer care. In resource scarce countries like Nepal, determining anti-emetic combinations of highest value is of utmost importance. The purpose of the study was to compare the efficacy and toxicity of Olanzapine (OLN) (a higher cost drug) and Haloperidol (HAL) (a lower cost drug) in the prevention of CINV in patients (pts) receiving highly emetogenic chemotherapy (HEC) in a developing country. Methods: An IRB approved randomized phase II trial was performed in chemotherapy-naive pts receiving cisplatin ≥70 mg/m² or cyclophosphamide ≥ 500 mg/m² and doxorubicin ≥ 50 mg/m². Pts were randomized to receive OLN 10 mg orally on day 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg BID on days 2 to 4. Both groups received ondansetron (OND) 16 mg and dexamethasone (DEX) 12 mg intravenously on day 1. Use of additional antiemetics for CINV refractory to assigned treatment arm was permitted. From day 1 to day 5, pts recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS). They also recorded their daily episodes of vomiting (number and when) and the use of additional antiemetics. The primary endpoint was complete nausea prevention (CNP) (ESAS - 0). The secondary endpoint was complete emesis prevention (CEP) without the use of additional antiemetics. Results: Sixty pts consented and were randomized, 30 in each arm. There was no difference in CNP during the overall period (day 1-5 post chemotherapy) between OLN and HAL (66.6% vs 70%; p = 0.78). In both the acute period (24 hours post chemotherapy) and delayed period (day 2-5 post chemotherapy) CNP was similar between OLN and HAL (acute - 83.3% vs. 80.0%; delayed - 66.6% vs. 73.3%). No difference was identified in the rate of CEP during the overall period (80% OLN vs. 76.6% HAL; p = 0.75) nor in the acute period ( 93.3% OLN vs. 90% HAL) or delayed period (83.3% OLN vs. 83.3% HAL). No difference in toxicities was noted between treatment arm. Conclusions: In this study, HAL was comparable to OLN in the control of CINV with no statistically significant difference in the primary and secondary endpoints suggesting it is the higher value option in pts receiving HEC in a resource scarce country.