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Human health in Odisha is directly vulnerable to climate change in the form of mortality as a result of climate-induced natural disasters (CINDs) and heatwaves. More frequent and intensified CIND has become an inevitable part of the state and its impact on human health has been detrimental. The magnitude of the impact of climate change on human health depends on the vulnerability and adaptation approaches of the state. The objectives of the paper are to study the changing pattern of climatic variability over 20 years in the state and to analyze the direct impact of climate change on human health in Odisha. Linear trend analysis is performed for annual average, pre-monsoon, monsoon, and post-monsoon rainfall as well as annual maximum and minimum temperature and for the heatwave period to show the changing pattern of climate in the state over 20 years. Regression analysis is performed between the indexed value of vulnerability and adaptation coefficients considered in the study as independent variables and mortality due to CIND as the dependent variable to analyze the impact of climate change on human health in the state. Also, correlation analysis is conducted to show the association between heatwave mortality and the maximum temperature of the heatwave period. The rainfall trend of the state for 20 years from 2000 to 2020 is found to increase in pre-monsoon and post-monsoon periods, while the annual average rainfall of the state for 20 years is slightly increasing and the monsoon period rainfall has remained consistent throughout the years. The annual maximum and minimum temperature and the heatwave period are found to be increasing. The regression analysis has shown a significant positive relationship between vulnerability coefficients and mortality as a direct impact of CIND on human health, whereas adaptation coefficients exhibit negative relation with it. Also, there is a moderate but significant association between the maximum temperature of the heatwave period with heatwave mortality. Odisha has been vulnerable to climate change during 2000–2020 as indicated by the high vulnerability score compared to the adaptation score for each year. However, years with better adaptive approaches, having high adaptive index scores, experienced less human mortality even with high vulnerability scores. [ABSTRACT FROM AUTHOR]