Objectives: Recent studies suggest that comprehensive smoking regulations to decrease exposure to second-hand smoke reduce the rates of acute myocardial infarction (AMI). The objective of this paper is to analyse if deaths due to AMI in Spain declined after smoking prevention legislation came into force in January 2006. Design: Information was collected on deaths registered by the Instituto Nacional de Estadistica for 2004e2007. Age- and sex-specific annual AMI mortality rates with 95% CIs were estimated, as well as age-adjusted annual AMI mortality rates by sex. Annual relative risks of death from AMI were estimated with an age-standardised Poisson regression model. Results: Adjusted AMI mortality rates in 2004 and 2005 are similar, but in 2006 they show a 9% decline for men and a 8.7% decline for women, especially among those over 64 years of age. In 2007 there is a slower rate of decline, which reaches statistical significance for men (-4.8%) but not for women (-4%). The annual relative risk of AMI death decreased in both sexes (p<0.001) from 1 to 0.90 in 2006, and to 0.86 in 2007. Conclusion: The extension of smoke-free regulations in Spain was associated with a reduction in AMI mortality, especially among the elderly. Although other factors may have played a role, this pattern suggests a likely influence of the reduction in population exposure to second-hand smoke on AMI deaths.