Background and aims: The application of prone positioning with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) in non-intubation patients is increasing gradually, applying prone positioning for more high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) patients. This meta-analysis evaluates the efficacy and tolerance of prone positioning combined with non-invasive respiratory support in patients with AHRF or ARDS. Methods: We searched randomized controlled trials (RCTs) (prospective or retrospective cohort studies, RCTs and case series) published in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 1 July 2020. We included studies that compared prone and supine positioning with non-invasive respiratory support in awake patients with AHRF or ARDS. The meta-analyses used random effects models. The methodological quality of the RCTs was evaluated using the Newcastle–Ottawa quality assessment scale. Results: A total of 16 studies fulfilled selection criteria and included 243 patients. The aggregated intubation rate and mortality rate were 33% 95% confidence interval (CI): 0.26–0.42, I2 = 25%, 4% (95% CI: 0.01–0.07, I2 = 0%), respectively, and the intolerance rate was 7% (95% CI: 0.01–0.12, I2 = 5%). Prone positioning increased PaO2/FiO2 mean difference (MD) = 47.89, 95% CI: 28.12–67.66; p < 0.00001, I2 = 67% and SpO2 (MD = 4.58, 95% CI: 1.35–7.80, p = 0.005, I2 = 97%), whereas it reduced respiratory rate (MD = −5.01, 95% CI: −8.49 to −1.52, p = 0.005, I2 = 85%). Subgroup analyses demonstrated that the intubation rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 34% and 21%, respectively; and the mortality rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 6% and 0%, respectively. PaO2/FiO2 and SpO2 were significantly improved in COVID-19 patients and non-COVID-19 patients. Conclusion: Prone positioning could improve the oxygenation and reduce respiratory rate in both COVID-19 patients and non-COVID-19 patients with non-intubated AHRF or ARDS. The reviews of this paper are available via the supplemental material section.