Objective To compare the sequential efficacy of high-flow nasal cannula oxygen therapy (HFNC) with non-invasive mechanical ventilation (NIV). Methods Randomized controlled trials comparing the efficacy of NIV sequential invasive mechanical ventilation with HFNC were included in the Chinese Journal Full-text Database, VIP Journal database, Wanfang Database, Chinese Biomedical Literature Database, PubMed, Cochrane Library and Embase. Meta-analysis was performed using RevMan5.4 software. Results A total of 2404 subjects were included in 19 studies. Meta-analysis results showed that compared with NIV, HFNC had a statistically significant difference in reducing patients' re-intubation rate in invasive mechanical ventilation sequence [relative risk (RR)=0.65, 95% confidence interval (CI) 0.50 - 0.86, Z=3.10, P=0.002]. HFNC showed statistically significant difference compared with NIV in reducing lung infection rate (RR=0.40, 95%CI 0.21 - 0.79, Z=2.67, P=0.008). HFNC was significantly different from NIV in terms of length of stay in Intensive Care Unit (ICU) (MD=–5.77, 95%CI –7.64 - –3.90, Z=6.05, P<0.00001). HFNC was significantly different from NIV in improving 24 h oxygenation index (MD=13.16, 95%CI 8.77 - 17.55, Z=5.87, P<0.00001). There was no significant difference in ICU mortality between HFNC and NIV (RR=0.70, 95%CI 0.45 - 1.08, Z=1.61, P=0.11). Conclusion Compared with NIV, sequential application of HFNC in invasive mechanical ventilation can improve the reintubation rate and pulmonary infection rate to a certain extent, reduce the length of ICU stay and improve the 24 h oxygenation index, while there is no difference in ICU mortality, which is worthy of clinical application.