Aim To investigate the relationship between plasma peroxiredoxin 5 (Prx5) level and prognosis in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods 148 ACS patients who received treatment from May 2016 to August 2017 were selected as the research objects, and the average follow-up time was 21.97 (8～24) months. Patients with ACS were divided into high Prx5 group (≥44.12 μg/L, n＝78) and low Prx5 group (＜44.12 μg/L, n＝70) according to the best cutoff point for evaluating the prognosis of ACS patients by Prx5. The plasma Prx5 level in ACS patients was detected by enzyme-linked immunosorbent assay, and its relationship with the prognosis of ACS patients after PCI was analyzed. Results Major adverse cardiovascular event (MACE) occurred in 32 (21.62%) patients with ACS. The area under the receiver operating characteristic curve, sensitivity, and specificity of Prx5 in evaluating the prognosis of patients with ACS were 0.3,3.75%, and 62.93%, respectively. The incidence of MACE in the high Prx5 group was lower than that in the low Prx5 group (P＜0.001). The average survival time of the high Prx5 group was 23.69 months (95%CI:23.34～24.04), which was higher than 20.06 months (95%CI:18.84～21.28) in the low Prx5 group (P＜0.001). COX univariate and multivariate analysis results showed age (HR＝1.1,5%CI:1.013～1.070, P＝0.005), family history of ACS (HR＝2.9,5%CI:1.022～5.677, P＝0.046) and history of chronic obstructive pulmonary disease (HR＝6.2,5%CI:1.953～19.700, P＝0.002) were independent risk factors for the prognosis of ACS patients, while Prx5 (HR＝0.1,5%CI:0.823～0.921, P＜0.001) was an independent protective factor for the prognosis of ACS patients. Conclusion Plasma Prx5 level is closely related to the prognosis of ACS patients after PCI, and the detection of Prx5 level is helpful to understand the prognosis.