Background The risk of peripherally inserted central catheter (PICC)-related complications in patients hospitalized with solid tumors remains unclear. Existing studies are limited by single-center, outpatient designs and include heterogenous patients. Methods A retrospective cohort study was designed and included adult patients with solid organ cancers who were admitted to a general medicine ward or intensive care unit and received a PICC. Data were collected from November 2013 to December 2019 at 50 Michigan hospitals. Major complications were defined as central line-associated bloodstream infection, deep vein thrombosis, pulmonary embolism, and catheter occlusion. Hospital variation in PICC use and outcomes was examined. Results Data included 3235 hospitalized patients with solid tumors who had PICCs placed for 51,047 catheter days. Most catheters were double-lumen devices (57.0%). Notably, 17.5% of patients had another central venous catheter at the time of PICC insertion. The most common indications for PICC use were antibiotics (34.5%) and difficult access or blood draws (21.6%); chemotherapy was the primary indication in only 15.7% of patients. A major PICC-related complication occurred in 491 patients (15.2%); catheter occlusion was the most prevalent complication (n = 322; 10.0%) followed by deep vein thrombosis (n = 116; 3.6%), central line-associated bloodstream infection (n = 82; 2.5%), and pulmonary embolism (n = 20; 0.6%). Significant variation in indications for PICC use, device characteristics, and frequency of major complications across hospitals was observed (p < .001). Conclusions PICCs were associated with significant complications in hospitalized patients who had solid malignancies and were often used for reasons other than chemotherapy. Policies and guidance for the appropriate use of PICCs in oncologic patients appear necessary. Lay summary Peripherally inserted central catheters (PICCs) are devices placed in peripheral veins to deliver medication to large veins near the heart. PICCs are used frequently in oncology. The objective of this report was to describe PICC-associated complications in hospitalized patients with solid tumors. This study was performed across 50 Michigan hospitals and included 3235 patients with solid tumor cancers and who had a PICC. Overall, 15.2% of patients experienced a complication, including central line-associated bloodstream infections, deep vein thrombosis, pulmonary embolism, or catheter occlusion. Complication rates varied across hospitals. PICCs are associated with substantial complications in hospitalized patients with solid tumors.