ObjectiveEnfortumab vedotin (EV) was approved for advanced urothelial carcinoma (UC) in 2021 after the EV‐301 trial showed its superiority to non‐platinum‐based chemotherapy as later‐line treatment after platinum‐based chemotherapy and immune checkpoint inhibitors including pembrolizumab. However, no study has compared EV with rechallenging platinum‐based chemotherapy (i.e., “platinum rechallenge”) in that setting.MethodsIn total, 283 patients received pembrolizumab for advanced UC after platinum‐based chemotherapy between 2018 and 2023. Of them, 41 and 25 patients received EV and platinum rechallenge, respectively, as later‐line treatment after pembrolizumab. After excluding two patients with EV without imaging evaluation, we compared oncological outcomes, including progression‐free survival (PFS) and overall survival (OS), between the EV (n = 39) and platinum rechallenge groups (n = 25) using propensity score matching (PSM).ResultsAnalyses on crude data (n = 64) showed no significant differences between the two groups regarding patients' baseline characteristics. PFS (5 months) and OS (11 months) in the EV group were comparable to those (8 and 12 months, respectively) in the platinum rechallenge group. After PSM (n = 36), the baseline characteristics between the two groups became more balanced, and PFS (not reached) and OS (not reached) in the EV group were comparable to those (8 and 11 months, respectively) in the platinum rechallenge group.ConclusionsEV and platinum rechallenge showed equivalent oncological outcomes, even after PSM, and both treatments should therefore be effective treatment options for post‐platinum, post‐pembrolizumab advanced UC.