Background: During coronavirus disease 2019 (COVID-19) pandemic, Helmet Continuous Positive Airway Pressure (h-CPAP) has been widely used to treat Acute Hypoxemic Respiratory Failure (AHRF). In COVID-19 patients undergoing h-CPAP a simple short peripheral catheter could be insufficient. According to the European Recommendations for Proper Indication and Use of Peripheral venous access consensus, a stable peripheral Vascular Access Device is indicated for intravenous treatment compatible with the peripheral route scheduled for more than 1 week. Objective: The aim of this prospective study was to evaluate the performance and the potential complications of superficial femoral midline catheters (SFMC) inserted in the Superficial Femoral Vein by direct Seldinger technique with peripheral tip (Arrow®, Teleflex; 20 cm length four FR single lumen and seven FR dual lumen) in AHRF COVID-19 patient. Complications were divided in early (accidental puncture of superficial femoral artery (APSFA); accidental saphenous nerve puncture (ASNP); bleeding) and late (Catheter Related Thrombosis (CRT); Catheter-Related Bloodstream Infections (CRBSI); Accidental Removal (AR); persistent withdrawal occlusion (PWO)). Methods: From 1st October 2020 to 30th June 2021 we conducted a prospective observational study in COVID-19 sub-intensive wards at Luigi Sacco Hospital (Milan). Results: Hundred seventy five SFMC (mean dwell time 11.1 ± 9.8 days) were implanted in COVID-19 patients, 107 (61.1%) during h-CPAP treatment (10.5 ± 8.9 days), the remaining 68 (38.9%) in patients with severe disease. We recorded two minor immediate/early complications (APSFA without sequelae) and no major complications. The long-term follow-up registered four CRBSI (2.3%–2.5/1000 catheters days (CD)), five CRT (2.9%: 2.6/1000 CD), 22 AR (12.6%; 11.4/1000 CD), 38 PWO (36.5%), 34 of which occurred due to fibroblastic sleeve (32.7%). Conclusions: SFMC proved to be safe, easy and time-saving. It could be implemented, after a careful benefits and risks evaluation, in particular settings such as h-CPAP, delirium, bleeding risk factors and palliative care patients.