Background: The association of culprit lesion location with short-term outcomes in patients presenting with ST-elevation myocardial infarction (STEMI) undergoing primary PCI is not well-described in contemporary era. Methods: We retrospectively analysed 3,283 patients with STEMI enrolled in the Victorian Cardiac Outcomes Registry. Multivariable logistic regression was used to assess the effect of proximal lesion location (located prior to the first major branch of the three coronary arteries) versus non-proximal location (lesion located elsewhere) on in-hospital and 30-day MACE (composite of mortality, myocardial infarction, stent thrombosis or unplanned coronary revascularisation). Results: Compared to the non-proximal group (n = 1,907, 58%), the proximal group (n = 1,376, 42%) presented with more cardiogenic shock (12.4% vs. 5.7%), out-of-hospital arrest (11.8% vs. 7.9%) and received more mechanical circulatory support (5% vs. 2.8%), all p-values <0.01. The proximal cohort had more left ventricular dysfunction (defined as moderate or severe dysfunction) (31.8% vs. 18.2%), more in-hospital renal impairment (5.9% vs. 3.7%) and higher peak CK (1804 IU/L vs. 1299 IU/L), all p-values <0.01. Excess in-hospital MACE (10.5% vs. 6.5%, p value <0.001) and 30-day MACE (12.3% vs. 8.2%, p value < 0.001) were observed in the proximal group. However, following multivariable adjustment, proximal lesion location was no longer an independent predictor of 30-day MACE (HR 1.23, 95% CI 0.92–1.65, p = 0.16). Conclusion: Despite the presence of higher risk characteristics among patients with proximal lesion location presenting with STEMI, culprit lesion location was not associated with worse outcomes at 30 days in the contemporary era of PCI and adjunctive medical therapy.