Aim To investigate the relationship between plasma receptor interaction protein kinase 3 (RIPK3) and prognosis in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods A total of 287 ACS patients who were treated from November 2016 to November 2017 were selected as the study objects prospectively. Enzyme-linked immunosorbent assay was used to detect the level of RIPK3 in plasma and its relationship with prognosis was analyzed. Results The incidence of major adverse cardiovascular events (MACE) during follow-up of 287 patients with ACS was 23.00%. Plasma RIPK3 levels in patients with ACS with MACE were higher than those with non MACE, and the difference was statistically significant (P＜0.05). The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity of RIPK3 in predicting the prognosis of patients with ACS were 0.8,4.85%, and 95.02%, respectively. The incidence of poor prognosis in the high RIPK3 group was higher than in the low RIPK3 group, and the difference was statistically significant (P＜0.05). The median survival time of ACS patients in high-RIPK3 group was lower than that in low-RIPK3 group, and the difference was statistically significant (P＜0.05). COX regression analysis showed that chronic obstructive pulmonary disease, time from onset to consultation, total bilirubin, and RIPK3 were closely related to the prognosis of patients with ACS. Conclusion Plasma RIPK3 is closely related to the prognosis of patients with ACS. Detection of plasma RIPK3 level is helpful to understand the prognosis of patients.