ObjectivesSeveral observational studies have suggested an association between high temperatures and all-cause mortality. However, estimates on more specific mortality outcomes are sparse, and frequently assessed in studies using different analytical methods.MethodsA time series analysis was performed on 10 regions in England and Wales during the summers (June–September) of 1993–2006. Average percentage linear increases in risk for a 1°C increase in temperature above region-specific thresholds and attributable deaths were computed by cause-specific mortality and age groups (0–64, 65–74, 75–84, 85+).ResultsThere was evidence of increased mortality with heat for almost all cause-of-death groups examined, with an overall increase in all-cause mortality of 2.1% (95% CI 1.6% to 2.6%) for a 1°C rise above the regional heat threshold. Among main causes, the steepest increase in risk was for respiratory mortality (+4.1% (3.5% to 4.8%) per 1°C). It was much smaller for cardiovascular causes (+1.8% (1.2% to 2.5%)) and myocardial infarction (+1.1% (0.7% to 1.5%)), but comparatively high for arrhythmias (+5.0% (3.2% to 6.9%)) and pulmonary heart disease (+8.3% (2.7% to 14.3%)). Among non- cardiorespiratory causes, the strongest effects were for genitourinary (+3.8% (2.9% to 4.7%)) and nervous system (+4.6% (3.7% to 5.4%)) disorders. 33.9% of heat deaths were attributable to cardiovascular causes, 24.7% to respiratory causes and 41.3% to all other causes combined.ConclusionsThese results suggest that the risk of heat-related mortality is distributed across a wide range of different causes, and that targeting of preventative actions based on pre-existing disease is unlikely to be efficient.