CONTEXT: Tobacco smoke includes a mix of carcinogens implicated in the etiology of bladder cancer (BC) and renal cell cancer (RCC). OBJECTIVE: We reviewed the impact of tobacco exposure on BCC and RCC incidence and mortality, and whether smoking cessation decreases the risk. EVIDENCE ACQUISITION: A systematic review of original articles in English was performed in August 2013. Meta-analysis of risks was performed using adjusted risk ratios where available. Publication bias was assessed using Begg and Egger tests. EVIDENCE SYNTHESIS: We identified 2683 papers, of which 107 fulfilled our inclusion criteria, of which 83 studies investigated BC and 24 investigated RCC. The pooled relative risk (RR) of BC incidence was 2.58 (95% confidence interval [CI] 2.37-2.80) for all smokers, 3.47 (3.07-3.91) for current smokers, and 2.04 (1.85-2.25) for former smokers. The corresponding pooled RR of BC disease-specific mortality (DSM) was 1.47 (1.24-1.75), 1.53 (1.12-2.09) and 1.44 (0.99-2.11). The pooled RR of RCC incidence was 1.31 (1.22-1.40) for all smokers, 1.36 (1.19-1.56) for current smokers, and 1.16 (1.08-1.25) for former smokers. The corresponding RCC DSM risk was 1.23 (1.08-1.40), 1.37 (1.19-1.59), and 1.02 (0.90-1.15). CONCLUSIONS: We present an up-to-date review of tobacco smoking and BC and RCC incidence and mortality. Tobacco smoking significantly increases the risk of BC and RCC incidence. BC incidence and DSM risk are greatest in current smokers and lowest in former smokers, indicating that smoking cessation confers benefit. We found that secondhand smoke exposure is associated with a significant increase in BC risk. PATIENT SUMMARY: Tobacco smoking affects the development and progression of bladder cancer and renal cell cancer. Smoking cessation reduces the risks of developing and dying from these common cancers. We quantify these risks using the most up-to-date results published in the literature.