Conclusion: Increasing catheter size, prior deep vein thrombosis (DVT), and surgery lasting >1 hour identify patients at risk for peripherally inserted central catheter (PICC)-associated DVT. Summary: PICCs are safe and cost-effective for providing long-term intravenous access. PICC catheters, however, are also associated with the development of catheter-associated DVT. The authors sought to identify risk factors for PICC-associated DVT. This was a 1-year prospective observational study of PICC insertions in a 456-bed tertiary referral hospital with a level 1 trauma center. All patients with one or more PICC insertions were included. PICC catheters were placed by certified PICC team members using a consistent and replicated approach for vein selection and insertion. A total of 2014 PICCs were inserted during 1879 distinct hospitalizations in 1728 distinct patients, yielding a total of 15,115 days of PICC placement. Most catheters were placed in the right arm (76.9%), and most were placed in the basilic vein (74%). Most were double-lumen 5F (75.3%). Of the 2014 PICC insertions 60 in 57 distinct patients (3%) developed DVT in the cannulated or adjacent veins. Factors associated with PICC associated DVT included prior DVT (odds ratio [OR], 9.92; P < .001), use of double-lumen 5F catheters (OR, 7.54; P < .05), triple-lumen 6F catheters (OR, 19.5; P < .01), and prior surgery duration >1 hour (OR, 1.66; P = .1). Comment: Assessment for DVT in the patients in this study occurred only in symptomatic patients. Therefore, the actual true incidence of PICC-associated DVT is likely to be much higher than that documented. It is doubtful the clinical correlates associated with PICC-induced DVT (prior DVT and surgery lasting >1 hour) will have much impact on the selection of patients for PICC placement. Physicians may, however, choose to treat patients with these identified correlates with enhanced prophylaxis after PICC placement. The data would also suggest it is important to minimize the size of the catheter to reduce the development of symptomatic PICC-associated DVT.