Climate change is one of the biggest health threats facing humanity and can directly affect human health through heat waves. This study aims to evaluate excess deaths during heat waves between the summer months of 2004 and 2017 in Istanbul and to determine a definition of heat waves that can be used in the development of an early warning system, a part of prospective urban heat-health action plans. In this study, heat waves were determined using the Excess Heat Factor, an index based on a three-day-averaged daily mean temperature. The death rates during heat waves and non-heat wave days of the summer months were compared with a Z test of the difference of natural logarithms. Thirty heat waves were recorded in Istanbul during the summer months of 2004–2017. In 67% of the heat waves, the death rate was significantly higher than the reference period and 4281 excess deaths were recorded. The mortality risk was especially higher during heat waves of higher intensity. The study showed an excess risk of mortality during heat waves in Istanbul, and the findings suggest that the Excess Heat Factor could be an appropriate tool for an early warning system in Istanbul.