BackgroundAwake prone positioning has been widely used in non-intubated patients with acute hypoxic respiratory failure (AHRF) due to COVID-19, but the evidence is mostly from observational studies and low-quality randomized controlled trials (RCTs), with conflicting results from published studies. A systematic review of published high-quality RCTs to resolve the controversy over the efficacy and safety of awake prone positioning in non-intubated patients with AHRF due to COVID-19.MethodsCandidate studies were identified through searches of PubMed, Web of Science, Cochrane, Embase, Scopus databases from December 1, 2019 to November 1, 2022. Literature screening, data extraction and risk of bias assessment were independently conducted by two researchers.ResultsEight RCTs involving 2657 patients were included. Meta-analysis of fixed effects models showed that awake prone positioning did not increase mortality(OR = 0.88, 95%CI [0.72, 1.08]), length of stay in ICU (WMD = 1.14, 95%CI [-0.45, 2.72]), total length of stay (WMD = 0.11, 95%CI [-1.02, 1.23]), or incidence of adverse events (OR = 1.02, 95%CI [0.79, 1.31]) compared with usual care, but significantly reduced the intubation rate (OR = 0.72, 95%CI [0.60, 0.86]). Similar results were found in a subgroup analysis of patients who received only high flow nasal cannula (Mortality: OR = 0.86, 95%CI [0.70, 1.05]; Intubation rate: OR = 0.69, 95%CI [0.58, 0.83]). All eight RCTs had high quality of evidence, which ensured the reliability of the meta-analysis results.ConclusionsAwake prone positioning is safe and feasible in non-intubated patients with AHRF caused by COVID-19, and can significantly reduce the intubation rate. More studies are needed to explore standardized implementation strategies for the awake prone positioning.Trial registrationCRD42023394113.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12879-023-08393-8.