Introduction <p>Acute myocardial infarction is one of the leading causes of death in Spain and a contributor to productivity loss. This condition represents an economic burden, involving significant indirect costs. Our objective here is to estimate premature deaths and productivity losses due to acute myocardial infarction in Spain during the period 2013–2022.</p> Methods <p>Productivity costs were estimated using a simulation model based on the human capital method. Mortality rates, average salaries, and employment rates were collected for the entire study period.</p> Results <p>After the analysis, acute myocardial infarction was identified as the leading cause of premature deaths related to cardiovascular diseases, accounting for 24% over the 10-year period. Additionally, an annual average of 26,935 YPLPLL was determined, with total productivity losses estimated at €5574.31 million, showing an upward trend over the reference period 2013–2022.</p> Conclusions <p>The study concludes by emphasizing the economic burden associated with acute myocardial infarction, which can assist decision-makers in allocating resources more efficiently.</p>