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There is an unmet need to predict immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors. This study aimed to examine whether eosinophils can predict irAEs in metastatic urothelial carcinoma (mUC). In this multicenter cohort study, we retrospectively examined eosinophil before (baseline sample) and 3 weeks after treatment (3-week sample) in 124 patients with mUC treated with pembrolizumab between January 2018 and October 2024. We divided the patients into two groups depending on whether they had experienced an irAE (irAE group) or not (non-irAE group). The variation in eosinophil proportion from baseline to 3 weeks was significantly higher in the irAE group than in the non-irAE group (non-irAE, 2.4%-3.1%; irAE, 2.2%-4.3%; p < 0.05). Notably, the variation in eosinophils from baseline to 3 weeks in patients with bladder cancer was significantly higher in the irAE group than in the non-irAE group (non-irAE, 2.5%-2.8%; irAE, 1.9%-4.1%; p < 0.05), but not in upper urinary tract urothelial cancer (non-irAE, 2.2%-3.7%; irAE, 2.8%-4.4%; p = 0.97). The optimal cutoff value for eosinophils in patients with bladder cancer against the occurrence of any-grade irAEs was 5.0% (area under the curve = 0.655). Multivariable analyses showed that eosinophil levels ≥ 5.0% increased the risk of any-grade irAEs in patients with bladder cancer (odds ratio 3.61, 95% confidence interval, 1.00-13.0). An eosinophil proportion ≥ 5.0% may be an effective biomarker for evaluating pembrolizumab-induced irAEs in patients with mUC, particularly those with bladder cancer.