Objective To investigate the effects of multiple safety management model on improving the safety compliance of stroke patients. Methods This study used prospective control study. A total of 853 stroke patients collected since May 2013 to February 2014 were divided into control group with 438 cases and observation group with 415 cases according to admission time. The control group used the conventional model, the observation group accepted the multiple safety management model, factors were recorded including pathogenic condition, medicine assessment, safety education and functional training. Comparison of safety compliance, satisfaction and rate of adverse nursing events were made in two groups using prospective case-control study. Results The safety compliance was 49. 75% and 63. 68% in control and observation group respectively(χ2 =21. 19,P=0. 01). Rates of fall, bed-falling, pressure sore and unplanned extubation were 1. 99%, 1. 24%, 3. 23% and 5. 22% in control group and they were 0. 25%, 0. 00%, 0. 25% and 0. 75% in observation group (P<0. 01). In terms of satisfaction, the rates were 77. 63% and 92. 47% in control and observation group (χ2 =30. 06,P<0. 01). Conclusions Multiple safety management model contributes to the improvement of safety compliance, decreases adverse nursing events and increases satisfaction in stroke patients. Considering the advantages and operability, multiple safety managements are worth popularization in clinical nursing.