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Background Cisplatin is a vital chemotherapy agent used for diverse cancers, but it is notorious for causing severe nausea and vomiting. These side effects can lead to malnutrition, metabolic issues, and treatment withdrawal. This study compares ondansetron and metoclopramide to optimize management of these debilitating symptoms. Improving antiemetic strategies is essential, as uncontrolled vomiting significantly degrades patient quality of life and complicates the overall clinical care process.Methods Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, this meta-analysis compared ondansetron and metoclopramide for preventing chemotherapy-induced nausea and vomiting (CINV) in adult cancer patients receiving cisplatin-based chemotherapy. Inclusion was restricted to randomized controlled trials. Patients with existing cardiovascular or psychiatric issues were excluded to maintain focus. Ultimately, these trials assessed efficacy and safety across populations totaling 428 oncology patients.Results This meta-analysis of two clinical studies confirms that ondansetron is significantly more effective than metoclopramide for preventing chemotherapy-induced nausea and vomiting. Regarding complete response, pooled data from 369 patients yielded a Risk Ratio (RR) of 0.78, indicating that ondansetron reduces emetic event risks by approximately 22%. Although the Hainsworth study alone was non-significant, the combined forest plot ‘diamond’ shows a statistically significant advantage (P = 0.002) ( IDDF2026-ABS-0502 Figure 1. Complete response). Furthermore, the analysis of Treatment Failure solidifies these results. A pooled RR of 1.75 favors ondansetron with high statistical significance (P = 0.0006) (IDDF2026-ABS-0502 Figure 2. Treatment failure). Since the confidence interval (1.27, 2.41) does not cross the vertical line of unity, the evidence strongly suggests patients treated with ondansetron are much less likely to experience treatment failure. Consequently, ondansetron is established as the superior prophylactic option, providing better symptom control and lower therapy inadequacy risks compared to metoclopramide.Conclusions Ondansetron is superior to metoclopramide for preventing acute CINV during cisplatin-based treatments. Evidence indicates that ondansetron achieves higher complete response rates and significantly delays vomiting onset. Although metoclopramide may assist with delayed nausea, its overall efficacy is limited by more frequent adverse events and treatment failures. Consequently, ondansetron remains the more effective, safer primary choice for managing acute emesis in high-risk patients.Abstract IDDF2026-ABS-0502 Figure 1Abstract IDDF2026-ABS-0502 Figure 2