Background: PONV (Postoperative nausea and vomiting) is a consistent concern in subjects undergoing ambulatory surgery. Olanzapine is efficacious in preventing PONV in subjects undergoing highly emetogenic chemotherapy. However, existing literature data is scarce concerning the comparison of standard antiemetics to olanzapine to prevent PONV after general anesthesia. Aim: The present study aimed to comparatively assess the standard antiemetic characteristics of olanzapine to prevent post-discharge nausea and vomiting following propofol-based GA. Methods: The present study assessed 212 adult subjects aged 18-65 years undergoing highly emetogenic daycare surgeries under propofol-based general anesthesia. Group I subjects were given preoperative 10 mg oral olanzapine, and Group II served as a control and administered 4mg ondansetron and 8mg intravenous dexamethasone intraoperatively. Primary outcomes assessed were nausea (NRS >3) and/or vomiting 24 hours following discharge. Secondary outcomes were PACU nausea and vomiting, side effects, and vomiting and nausea. Results: The severity and incidence of postoperative nausea and vomiting were similar in both the study groups in PACU with eight subjects feeling nausea and vomiting and 6 subjects had severe symptoms in Group I (olanzapine) with p=0.06 and post-discharge, 6 subjects had nausea and vomiting in Group I (Olanzapine) compared to 10 subjects in the control group with eight depicted as severe with p=0.482. The side effects including lightheadedness, dizziness, and sedation were statistically comparable in the two study groups. Conclusion: The present study concludes that a single postoperative olanzapine can be an efficacious alternative to standard antiemetic prophylaxis involving ondansetron and dexamethasone for the prevention of PONV (pre-operative nausea and vomiting) in highly emetogenic daycare surgeries under propofol-based general anesthesia.