Heatwaves are one of the deadliest natural disasters that occur annually with thousands of people seeking medical attention. The spatio-temporal synchronization between peaks in disease manifestation and high temperature provides important insights into the seasonal timing of the heatwave and the response it may cause with respect to emergence, severity, and duration. The objectives of this study are to examine the association between hospitalizations due to heat stroke in older adults and heat in the United States (US) and explore synchronization with respect to heatwave sequence, time of arrival, and regional climate. Three large data sets were utilized: daily hospitalization records of the US elderly between 1991 and 2006, annual demographic summaries on Medicare beneficiaries maintained by the Centers for Medicare and Medicaid Services (CMS), and nationwide daily meteorological observations. We modeled seasonal fluctuations in health outcomes, such as the timing and intensity of the seasonal peak in hospitalizations using refined harmonic GLM for eight climatically similar regions. During the 16-year study period, there were 40,019 heat-related hospitalizations (HRH) in the conterminous US. The rates of HRH varied substantially across eight climatic regions: with the highest rate of 7.05 cases per million residents observed in areas with temperate arid summers and winters (TaTa) and the lowest rate of 0.67-in areas with cold moderately dry summers and arid winters (CdCa), where summer temperatures are about 18.3 degrees C and 12.1 degrees C, respectively. We detected 400 heatwaves defined as any day when the night time temperature is above its 90th percentile for the current and previous nights. The first seasonal heatwave in a season resulted in 4274 hospitalizations over 342 heatwave-days: 34.3% of 12,442 hospitalizations occurred in 26% of 1308 heatwave-days. The relative risks of increased HRH associated with the first and second heatwaves were 10.4 (95%CI: 8.5; 12.3) and 11.4 (95%CI: 9.6; 13.3), respectively, indicating the disproportional effects of early heatwave arrivals. The seasonal spike in heat stroke hospitalizations in regions with relatively similar annual temperatures, e.g. in areas with temperate moderately dry summers and winters (TdTa: 12.8 degrees C) and (TaTa: 11.1 degrees C) ranged between 4.5 (95%CI: 3.3; 5.5) and 11.0 (95%CI: 8.2; 14.9) cases per million residents, respectively, indicating substantial regional differences. The differences in heat-related hospitalizations and response to heatwaves are substantial among older adults residing in different climate regions of the conterminous US. The disproportionally high response to the early seasonal heatwave deserves special attention, especially in the context of prevention and decision support frameworks.