High-flow nasal cannula (HFNC) therapy is a non-invasive respiratory treatment characterized by high tolerability, which largely derives from the patient's comfort. The primary aim of this study was to explore whether the patient's perceived comfort was the same regardless of different approaches used to reach the target humidification temperature. The secondary aim was to assess the patient's perceived nasal dryness and humidity. This single-centre, pragmatic, randomized trial was registered at clinicaltrials.gov (NCT05688189). Patients in the intensive care unit (ICU) in need of HFNC therapy were randomly assigned to one of three study arms: a two-step increase (31 to 34 to 37°C), a one-step increase in temperature (34-37°C) or no temperature increase (started and remained at 37°C). The patients were asked to rate their perceived comfort, as well as their perceived nasal dryness and humidity on a scale from 1 (lowest value) to 5 (highest value). We enrolled 21 patients, aged 34-85 years. The mean (±1 standard deviation) comfort level was 3.3 (1.3) for patients who received a one-step increase, 3.1 (1.3) for those who received no increase and 2.7 (1.7) for those who received a two-step increase (p = .714). There was also no difference in nasal dryness (p = .05) or humidity (p = .612) across the study arms. Greater comfort was fairly correlated with less nasal humidity (ρ = -0.34, 95% confidence interval -0.68 to 0.07) but not with nasal dryness (ρ = 0.01, p = .94). After 30 min of HFNC therapy at a target temperature of 37°C, overall comfort was rated similarly in the three study arms. Additional studies are needed to accumulate evidence corroborating the findings of this study. The temperature of the mixture of air and oxygen is a fundamental component of HFNC therapy. A pragmatic approach irrespective of the initial temperature setting seems to yield a similar comfort score in hospitalized patients with mild respiratory failure because of extrapulmonary causes.