BACKGROUND: Most of the epidemiological studies that have examined the detrimental effects of ambient hot and cold temperatures on human health have been conducted in high-income countries. In India, the limited evidence on temperature and health risks has focused mostly on the effects of heat waves and has mostly been from small scale studies. Here, we quantify heat and cold effects on mortality in India using a nationally representative study of the causes of death and daily temperature data for 2001-2013. METHODS AND FINDINGS: We applied distributed-lag nonlinear models with case-crossover models to assess the effects of heat and cold on all medical causes of death for all ages from birth (n = 411,613) as well as on stroke (n = 19,753), ischaemic heart disease (IHD) (n = 40,003), and respiratory diseases (n = 23,595) among adults aged 30-69. We calculated the attributable risk fractions by mortality cause for extremely cold (0.4 to 13.8°C), moderately cold (13.8°C to cause-specific minimum mortality temperatures), moderately hot (cause-specific minimum mortality temperatures to 34.2°C), and extremely hot temperatures (34.2 to 39.7°C). We further calculated the temperature-attributable deaths using the United Nations' death estimates for India in 2015. Mortality from all medical causes, stroke, and respiratory diseases showed excess risks at moderately cold temperature and hot temperature. For all examined causes, moderately cold temperature was estimated to have higher attributable risks (6.3% [95% empirical confidence interval (eCI) 1.1 to 11.1] for all medical deaths, 27.2% [11.4 to 40.2] for stroke, 9.7% [3.7 to 15.3] for IHD, and 6.5% [3.5 to 9.2] for respiratory diseases) than extremely cold, moderately hot, and extremely hot temperatures. In 2015, 197,000 (121,000 to 259,000) deaths from stroke, IHD, and respiratory diseases at ages 30-69 years were attributable to moderately cold temperature, which was 12- and 42-fold higher than totals from extremely cold and extremely hot temperature, respectively. The main limitation of this study was the coarse spatial resolution of the temperature data, which may mask microclimate effects. CONCLUSIONS: Public health interventions to mitigate temperature effects need to focus not only on extremely hot temperatures but also moderately cold temperatures. Future absolute totals of temperature-related deaths are likely to depend on the large absolute numbers of people exposed to both extremely hot and moderately cold temperatures. Similar large-scale and nationally representative studies are required in other low- and middle-income countries to better understand the impact of future temperature changes on cause-specific mortality.