objective. To determine the patient- and device-specific risk factors for hospital-acquired peripherally inserted central venous catheter- related bloodstream infections (PICC BSIs) in adult patients. design. Nested case-control study. setting. Barnes-Jewish Hospital, a 1,252-bed tertiary care teaching hospital. patients. Adult patients with PICCs placed from January 1, 2006, through July 31, 2008. methods. PICC BSI cases were identified using the National Healthcare Safety Network definition. Uninfected control patients with PICCs in place were randomly selected at a 3: 1 ratio. Patient- and device-related variables were examined using multivariate analysis. results. The overall PICC BSI rate was 3.13 per 1,000 catheter-days. Independent risk factors for PICC BSIs included congestive heart failure (odds ratio [OR], 2.0 [95% confidence interval (CI), 1.26-3.17]; P p.003), intra-abdominal perforation (OR, 5.66 [95% CI, 1.76-18.19]; P =.004), Clostidium difficile infection (OR, 2.25 [95% CI, 1.17-4.33]; P p.02), recent chemotherapy (OR, 3.36 [95% CI, 1.15-9.78]; P =.03), presence of tracheostomy (OR, 5.88 [95% CI, 2.99-11.55]; P!.001), and type of catheter (OR for double lumen, 1.89 [95% CI, 1.15-3.10]; P =.01; OR for triple lumen, 2.87 [95% CI, 1.39-5.92]; P =.004). Underlying chronic obstructive pulmonary disease (OR, 0.48 [95% CI, 0.29-0.78]; P =.03) and admission to surgical (OR, 0.43 [95% CI, 0.24-0.79]; P =.006) or oncology and orthopedic (OR, 0.35 [95% CI, 0.13-0.99]; P =.05) services were less likely to be associated with having a PICC BSI. conclusions. We identified several novel factors related to PICC BSIs. These factors may inform preventive measures.