PurposeThe role of high-flow nasal therapy (HFNT) as compared to conventional oxygen therapy (COT) in immunocompromised patients admitted to intensive care unit (ICU) with acute respiratory failure (ARF) remains unclear. We conducted a systematic review and meta-analysis in order to address this issue. MethodsWe searched PubMed, Medline and Embase until November 7th, 2018. Randomized controlled trials (RCTs), non-randomized prospective and retrospective evidence were selected. Observational studies were considered for sensitivity analysis. Primary outcome was mortality rate; intubation rate was a secondary outcome. ResultsWe included four studies in the primary analysis: one RCT, two RCT's post-hoc analyses and one retrospective study. We found no significant difference in short-term mortality comparing HFNT vs. COT: 1) ICU: n = 872 patients, odds ratio (OR) = 0.80 [0.44,1.45], p = 0.46, I2 = 30%, p = 0.24; 2) 28-day: n = 996 patients, OR = 0.79 [0.45,1.38], p = 0.40, I2 = 52%, p = 0.12). Conversely, we found a reduction of intubation rate in the HFNT group (n = 1052 patients, OR = 0.74 [0.55,0.98], p = 0.03, I2 = 7%, p = 0.36). The inclusion of one observational study for sensitivity analysis did not grossly change results. ConclusionsWe found no benefit of HFNT over COT on mortality in immunocompromised patients with ARF. However, HFNT was associated with a lower intubation rate warranting further research.