Peri-procedural stroke (PPS) is an important complication in patients who underwent percutaneous coronary intervention (PCI). The extent to which PPS impacts mortality and outcomes remains to be defined. Consecutive patients who underwent PCI enrolled in the Victorian Cardiac Outcomes Registry (2014 to 2018) were categorized into PPS and no PPS groups. The primary outcome was 30-day major adverse cardiovascular events (MACEs) (composite of mortality, myocardial infarction, stent thrombosis, and unplanned revascularization). Of 50,300 patients, PPS occurred in 0.26% patients (n = 133) (71% ischemic, and 29% hemorrhagic etiology). Patients who developed PPS were older (69 vs 66 years) compared with patients with no PPS, and more likely to have pre-existing heart failure (59% vs 29%), chronic kidney disease (33% vs 20%), and previous cerebrovascular disease (13% vs 3.6%), p <0.01. Among those with PPS, there was a higher frequency of presentation with ST-elevation myocardial infarction (49% vs 18%) and out-of-hospital cardiac arrest (14% vs 2.2%), PCI by way of femoral access (59% vs 46%), and adjunctive thrombus aspiration (12% vs 3.6%), all p = <0.001. PPS was associated with incident 30-day MACE (odds ratio [OR] 2.97, 95% confidence intervals [CIs] 1.86 to 4.74, p <0.001) after multivariable adjustment. Utilizing inverse probability of treatment weighting analysis, PPS remained predictive of 30-day MACE (OR 1.91, 95% CI 1.31 to 2.80, p = 0.001) driven by higher 30-day mortality (OR 2.0, 95% CI 1.35 to 2.96, p = 0.001). In conclusion, in this large, multi-center registry, the incidence of PPS was low; however, its clinical sequelae were significant, with a twofold increased risk of 30-day MACE and all-cause death.