Recent randomized clinical trials have questioned the clinical benefits of thrombus aspiration (TA) in ST-segment elevation myocardial infarction (STEMI). Real-world data on TA and the efficacy of TA for various culprit lesions have not been sufficiently evaluated. This study mainly aimed to evaluate whether the clinical impact of TA depends on culprit lesions in the setting of STEMI. We surveyed the Tokyo Coronary Care Unit Network Registry, a prospective cohort study, between 2010 and 2014, which included 10,232 patients with STEMI. In-hospital deaths occurred in 538 patients (5.3%). Improved Thrombolysis in Myocardial Infarction flow was more frequently observed in patients who underwent TA than in those who did not (87 vs. 80%; p < 0.001). Univariate logistic regression analysis revealed that TA was associated with a lower in-hospital mortality rate [odds ratio (OR), 0.80; 95% confidential interval (CI), 0.66–0.96; p = 0.016]. However, the difference was not significant after multivariate logistic regression analysis (OR 0.95; 95% CI 0.71–1.17; p = 0.355). Only TA for the left circumflex (LCx) lesions was associated with a better prognosis (OR 0.38; 95% CI 0.21–0.72; p = 0.003). The effect persisted after adjustment (OR 0.50; 95% CI 0.25–0.99; p = 0.049) but was attenuated after analysis using inverse probability weighting (OR 0.97; 95% CI 0.93–0.99; p = 0.048). On the basis of the findings in a large Japanese cohort, a prognostic benefit of TA on in-hospital mortality was not observed. The effect of TA on the LCx lesions was marginally significant and limited. Therefore, TA is not recommended in Japanese patients with STEMI.