This work investigated the protective effect of esmolol combined with milrinone on cardiac function in septic shock patients. A retrospective analysis was made on 56 septic shock patients. The patients were randomly divided into milrinone and milrinone+esmolol groups, which received the milrinone and esmolol combined with milrinone treatment for three days, respectively. After treatment, the total effective rate in milrinone+esmolol group was significantly higher than milrinone group. Compared with milrinone group, in milrinone+esmolol group the mean arterial pressure, central venous pressure, heart rate, cardiac index and stroke volume index were increased, the heart rate and systemic vascular resistance index were decreased, the blood lactic acid level was decreased, and the serum creatine kinase isoenzyme, troponin I, N -terminal probrain natriuretic peptide, tumor necrosis factor alpha, interleukin-6 and hypersensitive C -reactive protein levels were decreased. In conclusion, esmolol combined with milrinone can improve the hemodynamics, mitigate the myocardial injury, and reduce the inflammatory response, thus enhancing the cardiac function in septic shock patients.