Midline catheters are recommended over peripherally inserted central catheters as short-term vascular access device for peripherally compatible infusates. We assessed the effectiveness and safety of midline catheters. Data from midline catheter placements from June 2016 to May 2019 at a tertiary-care Veterans Administration medical center were retrospectively collected. Patients were followed until catheter removal or death, whichever occurred first. The primary outcome was completion of intended therapy; secondary outcomes were catheter-related complications, including major (eg, catheter-related bloodstream infections [CRBSI] or venous thromboembolism [VTE]) and minor (eg, catheter occlusion, kinking, dislodgement) events. Of 115 midlines, 62 (53.9%) were for antibiotic infusion and 49 (32.6%) for difficult access. The median dwell time was 11 days (interquartile range, 5.5-19.5 days). Midline catheters lasted through completion of therapy in 93 patients (80.9%). Catheter-related complications occurred in 27 patients (23.5%), including catheter dislodgement in 10 patients (8.7%), catheter kinking in 8 (7.0%), and catheter occlusion in 3 (2.6%). Only 1 patient experienced a major complication, a deep venous thrombosis (0.9%). Midlines appear to be effective and safe for short-term vascular access in patients requiring peripherally compatible infusates. While the rate of major complications is low, minor complications that necessitate device removal are common.