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Background: Despite pervasive need for peripheral intravenous catheters, insertion is often difficult, and approximately two thirds fail prematurely. Midline catheters are an alternative long peripheral catheter, inserted in the upper arm, ideal for patients with difficult access. Aim: The aim of this study is to test feasibility of the protocol and compare the efficacy and safety of midline catheters to peripheral intravenous catheters. Design: A parallel‐group, pilot randomized controlled trial of adult medical/surgical hospitalized patients, from a single Australian referral hospital. Methods: Participants with difficult vascular access (≤2 palpable veins) and/or anticipated ≥5 days of peripherally compatible intravenous therapy were recruited between May 2019 and March 2020. Participants were randomized to (1) peripheral intravenous catheter or (2) midline catheter. Primary feasibility outcome measured eligibility, recruitment, protocol adherence, retention and attrition. Primary clinical outcomes measured device insertion failure and post‐insertion failure. Results: In total, n = 143 participants (71 peripheral intravenous catheters and 72 midline catheters) were recruited; n = 139 were analysed. Most feasibility criteria were met. Peripheral intravenous catheters had shorter functional dwell time, with higher incidence of post‐insertion failure compared to midline catheters. Conclusion: Midline catheters appear to be superior for patients with difficult vascular access or receiving prolonged intravenous therapy; a large, multi‐centre trial to confirm findings is feasible. Summary statement: What is already known about this topic? Peripheral intravenous catheters have endemically high incidence of complications.Midline catheters have been proposed as an alternative peripheral intravenous device, following recent advancements in catheter material and design.Few studies have compared safety and efficacy of contemporary midline catheters with peripheral intravenous catheters. What this paper adds: Midline catheters had a longer functional dwell time and lower incidence of post insertion‐failure, compared to peripheral intravenous catheters.Midline catheters appear safe; however, inserter skill appears to have critical influence on insertion success. The implications of this paper: This study established the feasibility and importance of a large, multicentre, randomized controlled trial to confirm findings.Future research should also focus on financial impacts, including cost‐efficiency.Policy makers should consider training specialist inserters to place midline catheters. [ABSTRACT FROM AUTHOR]