Background. The urinary tract is the most common source for Escherichia coli bacteremia. Mortality from E. coli urinary-source bacteremia is higher than that from urinary tract infection. Predisposing factors for urinary-source E. coli bacteremia are poorly characterized.Methods.In order to identify urinary-source bacteremia risk factors, we conducted a 12-month prospective cohort study of adult inpatients with E. coli bacteriuria that were tested for bacteremia within ±1 day of the bacteriuria. Patients with bacteremia were compared with those without bacteremia. Bacterial isolates from urine were screened for 16 putative virulence genes using high-throughput dot-blot hybridization.Results.Twenty-four of 156 subjects (15%) had E. coli bacteremia. Bacteremic patients were more likely to have benign prostatic hyperplasia (56% vs 19%; P =. 04), a history of urogenital surgery (63% vs 28%; P =. 001), and presentation with hesitancy/retention (21% vs 4%; P =. 002), fever (63% vs 38%; P =. 02), and pyelonephritis (67% vs 41%; P =. 02). The genes kpsMT (group II capsule) (17 [71%] vs 62 [47%]; P =. 03) and prf (P-fimbriae family) (13 [54%] vs 40 [30%]; P =. 02) were more frequent in the urinary strains from bacteremic patients. Symptoms of hesitancy/retention (odds ratio [OR], 7.8; 95% confidence interval [CI], 1.6-37), history of a urogenital procedure (OR, 5.4; 95% CI, 2-14.7), and presence of kpsMT (OR, 2.9; 95% CI, 1-8.2) independently predicted bacteremia.Conclusions.Bacteremia secondary to E. coli bacteriuria was frequent (15%) in those tested for it. Urinary stasis, surgical disruption of urogenital tissues, and a bacterial capsule characteristic contribute to systemic invasion by uropathogenic E. coli.