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INTRODUCTION: Principles of management for upper tract urothelial carcinoma (UTUC) are mostly derived from knowledge of lower tract urothelial carcinoma (LTUC), however recent research indicates that these may be disparate diseases. In this review, we sought to compare the responsiveness of these tumors to similar treatment, platinum-based chemotherapy used in the adjuvant setting. MATERIALS AND METHODS: PubMed, EMBASE, and Web of Science were searched using a systematic search strategy. Disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) in patients with LTUC and UTUC treated with adjuvant chemotherapy were compared. Review Manager V 5.3 was used for meta-analyses. RESULTS: Adjuvant chemotherapy was associated with improved DFS (HR 0.41, 95%CI 0.31–0.54), CSS (HR 0.29, 95%CI 0.17–0.50) and OS (HR 0.51, 95%CI 0.38–0.70) rates in LTUC. The effectiveness of adjuvant chemotherapy in UTUC was less pronounced with respect to DFS (HR 0.61, 95%CI 0.1–0.93) and CSS (HR 0.70, 95%CI 0.56–0.90) rates, and there was no effect on OS (HR 0.87, 95%CI 0.69–1.10). Differences in CSS and OS were significant (p < 0.0001) in favor of adjuvant chemotherapy for LTUC versus UTUC CONCLUSION: Despite similar histology, we found significant differences in responsiveness to adjuvant chemotherapy between LTUC and UTUC. This may add to the already growing knowledge that these are disparate diseases. Newer systemic treatments for urothelial carcinoma may prove more effective than platinum-based chemotherapy in the adjuvant setting for UTUC.