Aims: To investigate the long-term prognostic value of aspiration thrombectomy in conjunction with primary percutaneous coronary intervention (PCI) compared to conventional PCI in patients with non-ST-elevation myocardial infarction (NSTEMI). Methods: In the randomized TATORT-NSTEMI (Thrombus aspiration in thrombus containing culprit lesions in non-ST-elevation myocardial infarction) trial, NSTEMI patients with thrombus containing culprit lesions were randomized to either PCI with aspiration thrombectomy or conventional PCI. The endpoint was a combination of all-cause death, reinfarction and new congestive heart failure. Results: From 440 patients initially randomized, outcome data were available in 432 (98.2%) patients at a median follow-up of 4.9 (interquartile range [IQR] 4.4–5.0) years. Thrombectomy was associated with a significant reduction of the combined endpoint compared to conventional PCI (19.9% vs. 30.7%, p = 0.01). This finding was primarily driven by a reduced rate of reinfarction with thrombectomy (3.4% vs. 10.3%, p = 0.01). Thrombectomy was still independently associated with the combined endpoint after multivariable adjustment (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.30–0.76, p = 0.002). Findings were consistent across all analyzed subgroups (p values for interaction all ' 0.05). Conclusions: In NSTEMI, thrombus aspiration is associated with favorable clinical outcome during long-term follow-up. Clinical trial registration: NCT01612312.