Peripherally inserted central catheters (PICCs) are frequently used to deliver outpatient courses of intravenous therapy. However, the rates and risks of complication for this device have not been well-studied. Our objective was to determine the incidence and risk factors of PICC-related complications with a 1-year prospective observational study. All PICCs inserted in adult and pediatric patients at Memorial Sloan-Kettering Cancer Center (MSKCC) were followed prospectively. The device insertion team, inpatient nurses, and various home-care companies and outside institutions collected longitudinal data. Three hundred fifty-one PICCs were inserted during the study period and followed for a total of 10,562 catheter-days (median placement, 15 days; range, 1 to 487 days). Two hundred five PICCs (58%) were managed by home-care companies and outside institutions, and 146 PICCs (42%) were managed exclusively at MSKCC. For these 205 PICCs, 131 nurses from 74 home-care companies and institutions were contacted for follow-up clinical information. In all, 115 (32.8%) of 351 PICCs were removed as a result of a complication, for a rate of 10.9 per 1,000 catheter-days. Patients with hematologic malignancy or bone marrow transplant were more likely to develop a complication, whereas those with metastatic disease were less likely. Complications occur frequently among cancer patients with PICCs, and long-term follow-up is onerous. Despite a high complication rate, the ease of insertion and removal argues for continued PICC use in the cancer population.