OBJECTIVE Peripherally inserted central catheter (PICC) tip malposition is potentially associated with complications, and postplacement adjustment of PICCs is widely performed. We sought to characterize the association between central line–associated bloodstream infection (CLABSI) or venous thrombus (VT) and PICC adjustment. DESIGN Retrospective cohort study. SETTING University of Michigan Health System, a large referral hospital. PATIENTS Patients who had PICCs placed between February 2007 and August 2007. METHODS The primary outcomes were development of CLABSI within 14 days or VT within 60 days of postplacement PICC adjustment, identified by review of patient electronic medical records. RESULTS There were 57 CLABSIs (2.69/1,000 PICC-days) and 47 VTs (1.23/1,000 PICC-days); 609 individuals had 1, 134 had 2, and 33 had 3 or more adjustments. One adjustment was protective against CLABSI (P = .04), whereas 2 or 3 or more adjustments had no association with CLABSI (P = .58 and .47, respectively). One, 2, and 3 or more adjustments had no association with VT formation (P = .59, .85, and .78, respectively). Immunosuppression (P < .01), power-injectable PICCs (P = .05), and 3 PICC lumens compared with 1 lumen (P = .02) were associated with CLABSI. Power-injectable PICCs were also associated with increased VT formation (P = .03). CONCLUSIONS Immunosuppression and 3 PICC lumens were associated with increased risk of CLABSI. Power-injectable PICCs were associated with increased risk of CLABSI and VT formation. Postplacement adjustment of PICCs was not associated with increased risk of CLABSI or VT.