BACKGROUND: Heat is recognized as one of the deadliest weather-related phenomena. Although the impact of high temperatures on mortality has been a subject of extensive research, few previous studies have assessed the impact of population adaptation to heat. METHODS: We examined adaptation patterns by analyzing daily temperature and mortality data spanning more than a century in New York City. Using a distributed-lag nonlinear model, we analyzed the heat-mortality relation in adults age 15 years or older in New York City during 2 periods: 1900-1948 and 1973-2006, to quantify population adaptation to high temperatures over time. RESULTS: During the first half of the century, the decade-specific relative risk of mortality at 29°C vs. 22°C ranged from 1.30 (95% confidence interval [CI]= 1.25-1.36) in the 1910s to 1.43 (1.37-1.49) in the 1900s. Since the 1970s, however, there was a gradual and substantial decline in the relative risk, from 1.26 (1.22-1.29) in the 1970s to 1.09 (1.05-1.12) in the 2000s. Age-specific analyses indicated a greater risk for people age 65 years and older in the first part of the century, but there was less evidence for enhanced risk among this older age group in more recent decades. CONCLUSION: The excess mortality with high temperatures observed between 1900 and 1948 was substantially reduced between 1973 and 2006, indicating population adaption to heat in recent decades. These findings may have implications for projecting future impacts of climate change on mortality.