Background: Patients undergoing radical cystectomy are at risk of developing venous thromboembolic events (VTE), with most VTEs occurring during neoadjuvant chemotherapy. The ASCO Clinical Practice Guideline Update recommends thromboprophylaxis in cancer patients with a high risk of VTE and a low risk of bleeding. However, the risks of VTE and bleeding with or without thromboprophylaxis in bladder cancer patients scheduled for radical cystectomy have not been well evaluated. Methods: We conducted a retrospective cohort study of patients with non-metastatic bladder cancer undergoing cystectomy across 28 centers in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis during neoadjuvant chemotherapy on VTE and bleeding. Results: Of 4886 patients, 4631 (95%) received neither thromboprophylaxis nor anticoagulation during chemotherapy. Thromboprophylaxis during neoadjuvant chemotherapy was prescribed in 151 (3%) patients mainly being enoxaparin (80%) with a median duration of 94 (range 38 to 104) days. In inverse probability weighting analyses, patients with thromboprophylaxis compared to patients without thromboprophylaxis during chemotherapy had not only a lower VTE (HR 0.32 [95% CI, 0.12 to 0.81], p-value = 0.016) but also a lower bleeding risk (HR 0.03 [95% CI, 0.09 to 0.12], p-value: <0.0001). Conclusions: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomized trials in other malignancies. Our data suggests thromboprophylaxis seems protective against VTEs during neoadjuvant chemotherapy in bladder cancer patients planned for cystectomy. The ASCO guidelines recommending thromboprophylaxis during chemotherapy should therefore also be regarded as a standard of care in patients treated with neoadjuvant chemotherapy before cystectomy.