Abstract Background The role of adhoc multi-vessel percutaneous coronary intervention (MV-PCI) in patients with ST elevation myocardial infarction (STEMI) and non ST elevation acute coronary syndromes (NSTE-ACS) has not fully defined yet. Therefore, we sought to evaluate the impact of MV-PCI on in-hospital outcome of patients with MV disease presenting with ACS. Methods and Results We evaluated 4, 457 haemodynamically stable patients with ACS and at least two major epicardial vessels with ≥ 70% stenosis of the contemporary Euro Heart Survey PCI registry. They were stratified into four categories: 419 STEMI and 734 NSTE-ACS patients undergoing MV-PCI and 2,118 STEMI and 1,186 NSTE-ACS patients undergoing culprit lesion (CL)-PCI only, respectively. In comparison to patients with CL-PCI hospital mortality was numerically lower among those undergoing MV-PCI for STEMI (1.4 versus 3.4%, P = 0.03) and for NSTE-ACS (1.1 versus 2.1%, P = 0.10). After adjustment for confounding variables no significant mortality difference was observed among patients treated with MV-PCI for STEMI (OR 0.48, 95%-CI 0.21–1.13) and for NSTE-ACS (OR 0.54, 95%-CI 0.24–1.22). However, the risk for non-fatal postprocedural myocardial infarction was markedly increased among patients undergoing MV-PCI for STEMI (8.8 versus 1.6%, P < 0.0001) and for NSTE-ACS (5.3 versus 1.8%, P < 0.0001). Conclusions In clinical practice MV-PCI in haemodynamically stable with ACS is used only in a minority of patients. There was no significant difference in hospital mortality between patients treated with MV- and CL-PCI, but MV-PCI was associated with a higher rate of postprocedural myocardial infarction.