Objective To investigate the effect of vasopressin on the prognosis in the patients with critical condition. Methods The basic information and clinical data of the patients in critical condition in American intensive care database Medical Information Mart for Intensive Care-Ⅲ(MIMIC-Ⅲ) were retrospectively analyzed. The influence of vasopressin on the prognosis of the patients in critical condition was investigated by propensity score matching method and Cox multivariate regression analysis. Results A total of 57 785 patients in critical condition were selected from the MIMIC-Ⅲ database, in which 2 171 were treated with vasopressin. Propensity matching method was used to match 1∶1 between the patients treated with vasopressin and the patients treated without vasopressin. A total of 1 168 patients were successfully matched. The mortality of in-hospital, 30 d, 1-year and long-term in the group using vasopressin were higher than the group treated without vasopressin after matching, and the time staying in hospital and intensive care unit (ICU) were significantly longer in the vasopressin group after matching. Cox multivariate regression analysis showed that using vasopressin was an independent risk factor for increased in-hospital mortality[hazard ratio(HR)=2.44, 95% confidence interval(CI): 2.147-2.772, P<0.001], 30 d mortality (HR=2.205, 95% CI:1.940-2.505, P<0.001), 1-year mortality (HR=1.999, 95% CI: 1.781-2.242, P<0.001) and long-term mortality (HR=1.891, 95% CI: 1.698-2.107, P<0.001). Conclusions This study used propensity score matching method and Cox multivariate regression analysis to conduct a large sample retrospective study, and showed that the using vasopressin is an independent risk factor for the prognosis of the patients with critical condition.