Background: Unintentional injury was the leading cause of death and disability among individuals younger than 49 years globally in 2019. However, the association between serum CK-MB levels and clinical value in polytrauma patients with nonmyocardial contusion remains unclear. Methods: This was a single-center, retrospective study. Demographic and clinical data were extracted from the Hospital Information System (HIS) at the Third Xiangya Hospital of Central South University. A total of 287 patients were included in the study. Patients were divided into a normal group (CK-MB ≤25 U/L) and an abnormal group (CK-MB >25 U/L) based on a low CK-MB level. Further clinical and follow- up data were analyzed by using univariate and multivariate logistic regression.Finally, disease-free survival and overall survival were calculated by the Kaplan– Meier method. Results: Multivariate logistic regression demonstrated that CK-MB (OR: 1.023, 95% CI: 1.006-1.040) was an independent risk factor for predicting in-hospital mortality in polytrauma patients with nonmyocardial contusion. Compared with normal CK-MB levels, CK-MB elevation was associated with a longer length of ICU stay (7.38±13.13 vs. 3.16±5.86 days, P =0.004) and total length of hospital stay (24.73±23.04 vs. 18.29±14.63 days, P =0.015) and was more likely to result in arrhythmia during hospitalization (19.29% vs. 10%, P =0.048). Moreover, the follow-up data showed that patients with CK-MB elevation were more likely to have cardiopalmus after discharge (15.00% vs. 5.68%, P =0.027). Conclusion: Our findings suggested that elevated CK-MB played an important role in the prognosis of polytrauma patients with nonmyocardial contusion, and a higher level of CK-MB indicated a poor prognosis.