The purpose of this study was to determine whether the plethysmographic variability index ("PVi") can predict preload responsiveness in patients with nasal high flow (NHF) (>= 30 L/min) with any sign of hypoperfusion. "Preload responsiveness" was defined as a >= 10% increase in stroke volume (SV), measured by transthoracic echocardiography, after passive leg raising. SV and PVi were reassessed in preload responders after receiving a 250-mL fluid challenge. Twenty patients were included and 12 patients (60%) were preload responders. Responders showed higher baseline mean PVi (24% vs. 13%; P = 0.001) and higher mean PVi variation (Delta PVi) after passive leg raising (6.8% vs. -1.7%; P < 0.001). No differences between mean Delta PVi after passive leg raising and mean Delta PVi after fluid challenge were observed (6.8% vs. 7.4%; P = 0.24); and both values were strongly correlated (r = 0.84; P < 0.001). Baseline PVi and Delta PVi after passive leg raising showed excellent diagnostic accuracy identifying preload responders (AUROC 0.92 and 1.00, respectively). Baseline PVi >= 16% had a sensitivity of 91.7% and a specificity of 87.5% for detecting preload responders. Similarly, Delta PVi after passive leg raising >= 2% had a 100% of both sensitivity and specificity. Thus, PVi might predict "preload responsiveness" in patients treated with NHF, suggesting that it may guide fluid administration in these patients. NEW & NOTEWORTHY This is the first study that analyzes the use of noninvasive plethysmographic variability index (PVi) for preload assessment in patients treated with nasal high flow (NHF). Its results showed that PVi might identify preload responders. Therefore, PVi may be used in the day-to-day clinical decision-making process in critically ill patients treated with NHF, helping to provide adequate resuscitation volume.