Ambient high temperature is associated with death; however, heat-related risk of death has not been quantified systematically in Ontario, the most populous province in Canada. Less is known about cold-related risk in this population. Our objective was to quantify the health impact from cold and hot temperatures in Ontario. The study population consisted of all residents of Ontario who died between Jan. 1, 1996, and Dec. 31, 2010, from any nonaccidental cause. A case-crossover analysis was applied to assess the relation between daily temperature fluctuation and deaths from nonaccidental and selected causes in cold (December-February) and warm (June-August) seasons, respectively, adjusting for various potential confounders. Risk estimates were obtained for each census division, then pooled across Ontario. We examined potential effect modification for selected comorbidities and sociodemographic characteristics. In warm seasons, each 5°C increase in daily mean temperature was associated with a 2.5% increase in nonaccidental deaths (95% confidence interval [CI] = 1.3% to 3.8%) on the day of exposure (lag 0). In cold seasons, each 5°C decrease in daily temperature was associated with a 3.0% (95% CI 1.8% to 4.2%) increase in nonaccidental deaths, which persisted over 7 days (lag 0-6). The cold-related effects (lag 0-6) were stronger for cardiovascular-related deaths (any cardiovascular death: 4.1%, 95% CI 2.3% to 5.9%; ischemic heart disease: 5.8%, 95% CI 3.6% to 8.1%), especially among people less than 65 years of age (8.0%, 95% CI 3.0% to 13.0%). Conversely, heat most strongly increased respiratory-related deaths during admission to hospital (26.0%, 95% CI 0% to 61.4%). Across Ontario, each 5°C change in daily temperature was estimated to induce 7 excess deaths per day in cold seasons and 4 excess deaths in warm seasons. Heat contributed to excess deaths in Ontario, although the effect of cold weather appeared to be greater. Further work is required to better define high-risk subgroups, which might include the homeless and people with inadequately heated housing.