This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%–75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%–43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.