High thrombus burden, subsequent distal embolization, and myocardial no-reflow remain a large obstacle that may negate the benefits of urgent coronary revascularization in patients with ST-segment elevation myocardial infarction (STEMI). However, the biological function and clinical association of Hsp-27 with thrombus burden and clinical outcomes in patients with STEMI is not clear. Consecutive patients (n = 146) having STEMI undergoing primary percutaneous coronary intervention (pPCI) within 12 hours from the onset of symptoms were enrolled in this prospective study in the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, P.R. China. Patients were divided into low thrombus burden and high thrombus burden groups. The present study demonstrated that patients with high-thrombus burden had higher plasma Hsp-27 levels ([32.0 ± 8.6 vs. 58.0 ± 12.3] ng/mL, P < 0.001). The median value of Hsp-27 levels in all patients with STEMI was 45 ng/mL. Using the receiver operating characteristic (ROC) curve analysis, plasma Hsp-27 levels were of significant diagnostic value for high thrombus burden (AUC, 0.847; 95% CI, 0.775–0.918; P < 0.01). The multivariate cox regression analysis demonstrated that Hsp-27 > 45 ng/mL (HR 2.801, 95% CI 1.296–4.789, P = 0.001), were positively correlated with the incidence of major adverse cardiovascular events (MACE). Kaplan-Meier survival analysis demonstrated that MACE-free survival at 180-day follow-up was significantly lower in patients with Hsp-27 > 45 ng/mL (log rank = 10.28, P < 0.001).Our data demonstrate that plasma Hsp-27 was positively correlated with high thrombus burden and the incidence of MACE in patients with STEMI who underwent pPCI.