Recently, the first genome-wide association study of bladder cancer identified an association of genome-wide significance between single nucleotide polymorphism (SNP) rs715021 and urinary bladder cancer risk among European individuals. This SNP is in a haplotype block in linkage disequilibrium with the TP63 gene. We investigated the role of this SNP among 1,042 cases and 1,123 controls among non-Latino whites in Los Angeles County, CA and among Chinese in Shanghai, China. We confirmed an association between the A allele and bladder cancer risk [log-additive per A allele odds ratios (OR), 1.24; and 95% confidence intervals (95% CI), 1.02-1.52; P = 0.032] in Los Angeles County and a similar association in Shanghai (log-additive per A allele OR, 1.21; 95% CI, 0.98-1.49; P = 0.080). These estimates did not differ by study site, smoking status, or gender. However, the effects were greater in older individuals. Analysis within non-Latino whites, for whom we had histologic results, revealed that this association was restricted to low-risk tumors (OR, 1.49; 95% CI, 1.17-1.92; P = 0.002) and absent among high-risk tumors (OR, 1.03; 95% CI, 0.80-1.33; P = 0.790; heterogeneity, P = 0.019). A positive association (OR, 1.56; 95% CI, 0.93-2.62; P = 0.089) was only observed among high-risk tumors from individuals older than 56 years old (interaction, P = 0.045). Our results suggest that a TP63 gene variant may increase susceptibility for the development of urinary bladder tumors with low risk of progression.