Morbidity and mortality due to ischemic heart disease (IHD) is subject to wide geographic variation both between and within countries. The aim of this study was to determine whether geographic variations exist in the prevalence of metabolic syndrome in the Spanish working population or in its relationship with IHD mortality. We analyzed clinical and laboratory data obtained during health check-ups carried out in Spanish workers (n=17,837) during 2003. The prevalence of metabolic syndrome was 17% in men and 6.5% in women. However, there was a heterogeneous distribution across the different regions studied. The prevalence in southern and western regions (e.g., in men: 22.15% in Extremadura and 20.6% in Galicia) was double that observed in central and northern zones (e.g., in the Basque Country and Castile and León). This research indicates that there is a significant association between IHD mortality and the prevalence of metabolic syndrome in workers from different Spanish regions.