Purpose This article discusses the clinical therapeutic effect of recombinant human pro-urokinase combined with percutaneous coronary intervention in the treatment of acute ST‐segment elevation myocardial infarction. Method A retrospective analysis of 89 patients with acute ST‐segment elevation myocardial infarction admitted in our hospital from January to December 2020 was conducted and divided into the treatment group (n=46) and the control group (n=43) according to different treatment options. The control group was treated with percutaneous coronary intervention, and the treatment group was treated with recombinant human pro‐urokinase based on that. The levels of LVEF, LVEDD, CK‐MB, hs‐CRP, and coronary artery recanalization rates were compared between the two groups. Results Before the operation, there was no statistically significant difference in the levels of LVEF and LVEDD between the two groups (P>0.05). After the operation, the LVEF levels of the two groups increased, and the LVEDD levels decreased. The difference between the groups was not statistically significant (P>0.05). Similarly, before the operation, there was no significant difference in the levels of CK‐MB and hs‐CRP between the two groups (P>0.05). After the operation, the levels of CK‐MB and hs‐CRP in the two groups decreased, but the levels of the treatment group were lower than those of the control group. The difference between the groups was statistically significant (P<0.05). Conclusion Recombinant human pro‐urokinase combined with percutaneous coronary intervention can achieve better results in the treatment of acute ST‐segment elevation myocardial infarction, which can further reduce the levels of CK‐MB and hs‐CRP and increase the coronary recanalization rate.