A case-crossover study among 511,767 cardiovascular disease (CVD) deaths in Jiangsu province, China, during 2015-2021 was conducted to assess the association of exposure to ambient ozone (O(3)) and heat wave with CVD mortality and explore their possible interactions. Heat wave was defined as extreme high temperature for at least two consecutive days. Grid-level heat waves were defined by multiple combinations of apparent temperature thresholds and durations. Residential O(3) and heat wave exposures were assessed using grid data sets (spatial resolution: 1 km × 1 km for O(3); 0.0625° × 0.0625° for heat wave). Conditional logistic regression models were applied for exposure-response analyses and evaluation of additive interactions. Under different heat wave definitions, the odds ratios (ORs) of CVD mortality associated with medium-level and high-level O(3) exposures ranged from 1.029 to 1.107 compared with low-level O(3), while the ORs for heat wave exposure ranged from 1.14 to 1.65. Significant synergistic effects on CVD mortality were observed for the O(3) and heat wave exposures, which were generally greater with higher levels of the O(3) exposure, higher temperature thresholds, and longer durations of heat wave exposure. Up to 5.8% of the CVD deaths were attributable to O(3) and heat wave. Women and older adults were more vulnerable to the exposure to O(3) and heat wave exposure. Exposure to both O(3) and heat wave was significantly associated with an increased odds of CVD mortality, and O(3) and heat wave can interact synergistically to trigger CVD deaths.