Peripherally inserted central catheters (PICCs) are prevalent devices for medium-to-long-term intravenous therapy but are often associated with morbid and potentially lethal complications. This multi-center study sought to identify barriers and facilitators of implementing evidence-based appropriateness criteria to improve PICC safety and patient outcomes in a pay-for-performance model. Participating hospitals received an online toolkit with five recommendations: establishing a vascular access committee; implementing a clinical decision tool for PICC appropriateness; avoiding short-term PICC use (≤5 days); increasing use of single-lumen PICCs; and avoiding PICC placement in patients with chronic kidney disease. Longitudinal online surveys conducted biannually October 2014-November 2018 tracked implementation efforts. A total of 306 unique surveys from 34 hospitals were completed. The proportion of hospitals with a dedicated committee overseeing PICC appropriateness increased from 53% to 97%. Overall, 94% of hospitals implemented an initiative to reduce short-term and multi-lumen PICC use, and 91% integrated kidney function into PICC placement decisions. Barriers to implementation included: achieving agreement from diverse disciplines, competing hospital priorities, and delays in modifying electronic systems to enable appropriate PICC ordering. Provision of quarterly benchmarking reports, a decision algorithm, access to an online toolkit, and presence of local champion support were cited as crucial in improving practice. Structured quality improvement efforts including a multidisciplinary vascular access committee, clear targets, local champions, and support from an online education toolkit have led to sustained PICC appropriateness and improved patient safety.