Aim Trends in acute myocardial infarction (AMI) epidemiology and care at the population level provide insight into the effectiveness of healthcare systems. In this study, we aim to evaluate 25-year trends in AMI hospitalizations, management and outcomes, in the Veneto Region (Italy) population. Methods We conducted a retrospective, population-based analysis of all hospital discharge records from 2000 to 2024. AMI cases were classified as ST-Elevation myocardial infarction (STEMI) or Non-ST-Elevation myocardial infarction (NSTEMI) using ICD9-CM codes. Hospitalization rates, key care process indicators and 30-day mortality were estimated. The average annual percentage change (AAPC) and relative 95% confidence interval (CI) were calculated to identify trends. Results Over the study period, 167,277 patients were hospitalized for AMI in the Veneto Region. STEMI accounted for 57.3% of cases (mean age: 70.6 ± 13.9 years), and NSTEMI for the remaining 42.7% (mean age: 72.4 ± 12.8 years). Age-standardized hospitalization rates of AMI declined during the study period from 151.1 to 98.8 per 100,000 inhabitants [AAPC: −2.30%, (95% CI: −2.63 to −2.01), p<0.001], driven by reductions in STEMI [AAPC: −4.72%, (95% CI: −5.20 to −4.34), p<0.001], while NSTEMI increased [AAPC: +1.05%, (95% CI: 0.25 to 1.86), p=0.011] and became predominant from 2016 onward ( Figure 1 ). Admissions in specialized cardiology wards (ordinary or intensive care) increased over time, especially among STEMI patients [from 68.7% in 2000 to 85.1% in 2024; AAPC: +0.85% (95% CI: 0.68 to 1.03), p<0.001]. Moreover, same-day PCI among STEMI patients increased markedly from 8.0% in 2000 to 72.3% in 2024 [AAPC: +6.41%, (95% CI: 5.36 to 8.20), p<0.001] ( Figure 2 ). The age-standardized 30-day mortality rate declined continuously throughout the 25-year period both for STEMI (from 19.3% in 2000 to 13.2% in 2024) and for NSTEMI (from 10.0% to 5.1% in the same period) ( Figure 3 ). Conclusions Over 25 years, AMI in the Veneto Region shifted from STEMI- to NSTEMI-dominance, with improved procedural access and outcomes.