The main goal of primary percutaneous coronary intervention (PPCI) is to achieve not only restoration of flow in the epicardial coronary artery, but also reperfusion at the level of myocardial tissue. Distal embolization is a possible complication of PPCI; in these patients, a microvascular injury occurs, which finally leads to a lack of myocardial reperfusion. Thrombus aspiration during PPCI has been proposed to prevent embolization. Several different thrombectomy devices have been demonstrated to be well tolerated and effective in improving surrogate markers of myocardial reperfusion; furthermore, in a few studies, the use of thrombectomy was associated with an improvement of clinical outcome. Because study results appeared largely inconsistent, especially about clinical outcome data, several meta-analyses have been carried out, showing that thrombectomy is able to improve markers of myocardial reperfusion and that manual thrombectomy is associated with better results in terms of myocardial reperfusion and clinical outcome, compared with embolic protection or mechanical thrombectomy devices, probably due to its easy and time-sparing use with low rate of complication. Literature data, based mainly on the Thrombus Aspiration During Primary Percutaneous Coronary Intervention (TAPAS) trial, indicate a favourable effect on outcome of routine manual thrombectomy strategy and the recent European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) guidelines on myocardial revascularization recommend thrombus aspiration during PPCI. However, data on long-term clinical outcome are still inconsistent and no trials have been, at the present time, designed to assess hard endpoint. In this review, we have carefully analysed literature data on thrombectomy during PPCI, taking into account the most recent studies and the last meta-analyses; study results have been compared to verify if either a routine or a selective use of thrombectomy should be adopted and to assess whether the use of thrombectomy may finally improve clinical outcome.