BACKGROUND: Heatwaves pose significant risks to human health. Implementing heat health warning systems (HHWS) has been widely adopted as a preventive measure. However, the effectiveness of the German HHWS in reducing mortality during heat episodes across different cities has scarcely been researched. OBJECTIVE: This study aimed to assess the effect of HHWS on mortality during heat episodes in 15 major cities in Germany and explore city-specific factors influencing the effectiveness of heat alerts. METHODS: Daily all-cause mortality data during the warm-season months (May to September) from 1993 to 2020 were linked with heat alert data and meteorological information. A difference-in-differences approach was employed to estimate the city-specific effects of heat alerts on mortality. In the second stage, meta-regression models were used to pool the city-specific estimates and examine the heterogeneity across cities. RESULTS: Substantial variation in the city-specific associations was observed, with some cities exhibiting significant reductions in mortality during heat episodes after the HHWS implementation while others showed no significant effect. The pooled relative risk (RR) from the second-stage analysis, based on the meta-variables averaged across all cities studied, suggested no overall significant protective effect of heat alerts on mortality (RR = 1.00, 95 %CI:0.98 to 1.01). However, when controlling for the meta-variables recreational area per person, total population, and population density, we found a significant but small protective effect of heat alerts across all cities studied (RR = 0.85, 95 %CI:0.75 to0.97). CONCLUSION: According to our results, the effectiveness of heat alerts varied considerably across the cities, suggesting the importance of considering city-specific factors, such as population size, population density, and the presence of blue and green urban infrastructure. Understanding these factors can help improve the effectiveness of HHWS and tailor interventions to address the specific characteristics of different urban areas within heat-health action plans.