BACKGROUND: The optimal intravenous device for antibiotic administration for children with respiratory disease is uncertain. We assessed the feasibility of a randomized controlled trial (RCT) comparing midline catheters with peripherally inserted central catheters (PICCs). METHODS: Prospective, 2-arm, feasibility RCT in an Australian tertiary, pediatric hospital. Random assignment of 110 children (< 18 years) to receive (i) midline catheter, (ii) PICC. Primary outcome was feasibility (eligibility, recruitment, retention, protocol adherence and acceptability), and the primary clinical outcome was general anesthesia requirement for intravenous catheter insertion. SECONDARY OUTCOMES: insertion time, treatment delays, infusion efficiency, device failure, complications, and cost. RESULTS: There was 80% recruitment, 100% retention, no missing data, and high patient/staff acceptability. Mean patient experience assessed on a 0-10 numeric rating scale was 8.0 (PICC) and 9.0 (midline catheters) respectively. Participant eligibility was not achieved (49% of screened patients) and moderate protocol-adherence across groups (89% PICC vs 76% midline catheter). Insertion of midline catheter for pulmonary optimisation reduced the requirement for general anesthesia compared to PICCs (10% vs 69%; odds ratio=0.01, 95% confidence interval: 0.00-0.09). Midline catheters failed more frequently (18.1 vs 5.5 PICCs per 1,000 catheter-days), however this reduced over trial duration. Midline catheter insertion compared to PICCs saved AUD$1,451 per pulmonary optimisation episode. CONCLUSION: An efficacy trial is feasible with expanded eligibility criteria and intensive staff training when introducing a new device. Midline catheter for peripherally compatible infusions is acceptable to patients and staff, might negate the need for general anesthesia and results in significant cost savings.