Objective To systematically evaluate the risk factors for secondary respiratory failure (RF) on chronic obstructive pulmonary disease (COPD), so as to provide evidence for formulating prevention and control strategies. Methods PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP databases and SinoMed were searched for articles published from the dates of establishment of databases to August 2021. To collect the relevant case-control studies or cohort studies on the risk factors of secondary RF in patients with COPD. The patients were divided into two groups, RF group and non RF group. Meta-analysis was carried out with RevMan 5.3 software after selecting literature, extracting data and evaluating quality according to inclusion and exclusion criteria. Results A total of 16 case-control studies involving 2 417 patients were included. There were 856 cases in RF group and 1 561 cases in non RF group. The results of meta-analysis showed that age [mean difference (MD)=0.58 years, 95% confidence interval (CI) (0.18, 0.97) years, P=0.004], number of acute attacks per year [MD=2.68 times, 95%CI (2.58, 2.78) times, P<0.001], number of acute attacks per year over 3 [odds ratio (OR)=3.37, 95%CI (2.40, 4.73), P<0.001], serum albumin level [MD=−2.93 g/L, 95%CI (−3.92, −1.94), P<0.001], serum uric acid [MD= −59.91 mmol/L, 95%CI (−66.57, −53.25) mmol/L, P<0.001], nosocomial infection [OR=4.53, 95%CI (3.44, 5.98), P<0.001], no-inhaled glucocorticoid [OR=3.63, 95%CI (2.95, 4.48), P<0.001], acid-base imbalance [OR=13.22, 95%CI (10.14, 17.23), P<0.001], COPD very serious [OR=1.82, 95%CI (1.50, 2.21), P<0.001], cardiovascular disease [OR=2.73, 95%CI (1.99, 3.74), P<0.001], kidney disease [OR=3.62, 95%CI (2.67, 4.90), P<0.001] were risk factors for RF in COPD. Sensitivity analysis showed that the results of meta-analysis were stable. Conclusion According to the results of meta-analysis, the risk factors of secondary RF in COPD can be identified in time and preventive measures can be taken to effectively reduce the incidence of aspiration failure and improve the prognosis and outcome of patients.