Background Although important in clinical care, reports of inappropriate peripherally inserted central catheter (PICC) use are growing. Objective To test whether implementation of the Michigan Appropriateness Guide for Intravenous Catheters (MAGIC) can improve PICC use and patient outcomes. Design Quasi-experimental, interrupted time series design at one study site with nine contemporaneous external controls. Setting Ten hospitals participating in a state-wide quality collaborative from 1 August 2014 to 31 July 2016. Patients 963 hospitalised patients who received a PICC at the study site vs 6613 patients at nine control sites. Intervention A multimodal intervention (tool, training, electronic changes, education) derived from MAGIC. Measurements Appropriateness of PICC use and rates of PICC-Associated complications. Segmented Poisson regression was used for analyses. Results Absolute rates of inappropriate PICC use decreased substantially at the study site versus controls (91.3% to 65.3% (b '26.0%) vs 72.2% to 69.6% (b '2.6%); P<0.001). After adjusting for underlying trends and patient characteristics, however, a marginally significant 13.8% decrease in inappropriate PICC use occurred at the study site (incidence rate ratio 0.86 (95% CI 0.74 to 0.99; P=0.048)); no change was observed at control sites. While the incidence of all PICC complications decreased to a greater extent at the study site, the absolute difference between controls and intervention was small (33.9% to 26.7% (b '7.2%) vs 22.4% to 20.8% (b '1.6%); P=0.036). Limitations Non-randomised design limits inference; the most effective component of the multimodal intervention is unknown; effects following implementation were modest. Conclusions In a multihospital quality improvement project, implementation of MAGIC improved PICC appropriateness and reduced complications to a modest extent. Given the size and resources required for this study, future work should consider cost-To-benefit ratio of similar approaches.