A retrospective study of 106 patients with muscle-invasive bladder cancer (MIBC) has shown that tumour budding is an independent predictor of cancer-specific mortality. Tumour buds were identified and quantified on radical cystectomy samples using the hot-spot method. Mean tumour bud count was 32.3 ± 25.9 buds, with 14 buds being the cut-off point according to the receiver operating characteristic. Mean survival for participants with ≤14 buds was 65.9 months, but survival for those with >14 buds was only 18.5 months (P = 0.003). In multivariable analysis, number of tumour buds was an independent predictor of mortality. Patients with >14 buds had a 2.27-fold increased risk of mortality and the risk of mortality increased progressively with the number of buds at a rate of 2% per bud. Thus, tumour budding could be used as a predictor of cancer-specific mortality in patients with MIBC.