In this single-center, retrospective cohort study of 1169 patients requiring outpatient parenteral antimicrobial therapy, complications (i.e., bloodstream infections or venous thrombosis) occurred more frequently in patients with midlines (6.4 per 1,000 line-days) than peripherally inserted central catheters (1.1 per 1,000 line-days), adjusted hazard ratio 3.60 (95% confidence interval 1.66–7.81).