BACKGROUND: Studies assessing the effect of altitude on cardiovascular disease have provided conflicting results. Most studies were limited because of the heterogeneity of the population, their ecological design, or both. In addition, effects of place of birth were rarely considered. Here, we examine mortality from coronary heart disease and stroke in relation to the altitude of the place of residence in 1990 and at birth. METHODS AND RESULTS: Mortality data from 1990 to 2000, sociodemographic information, and places of birth and residence in 1990 (men and women between 40 and 84 years of age living at altitudes of 259 to 1960 m) were obtained from the Swiss National Cohort, a longitudinal, census-based record linkage study. The 1.64 million German Swiss residents born in Switzerland provided 14.5 million person-years. Relative risks were calculated with multivariable Poisson regression. Mortality from coronary heart disease (-22% per 1000 m) and stroke (-12% per 1000 m) significantly decreased with increasing altitude. Being born at altitudes higher or lower than the place of residence was associated with lower or higher risk. CONCLUSIONS: The protective effect of living at higher altitude on coronary heart disease and stroke mortality was consistent and became stronger after adjustment for potential confounders. Being born at high altitude had an additional and independent beneficial effect on coronary heart disease mortality. The effect is unlikely to be due to classic cardiovascular disease risk factors and rather could be explained by factors related to climate.