Several studies have examined the relationship of high and low air temperatures to cardiovascular mortality in the Czech Republic. Much less is understood about heat-/cold-related cardiovascular morbidity and possible regional differences. This paper compares the effects of warm and cold days on excess mortality and morbidity for cardiovascular diseases (CVDs) in the city of Prague and a rural region of southern Bohemia during 1994-2009. Population size and age structure are similar in the two regions. The results are evaluated for selected population groups (men and women). Excess mortality (number of deaths) and morbidity (number of hospital admissions) were determined as differences between observed and expected daily values, the latter being adjusted for long-term changes, annual and weekly cycles, and epidemics of influenza/acute respiratory infections. Generally higher relative excess CVD mortality on warm days than on cold days was identified in both regions. In contrast to mortality, weak excess CVD morbidity was observed for both warm and cold days. Different responses of individual CVDs to heat versus cold stress may be caused by the different nature of each CVD and different physiological processes induced by heat or cold stress. The slight differences between Prague and southern Bohemia in response to heat versus cold stress suggest the possible influence of environmental and socioeconomic factors such as the effects of urban heat island and exposure to air pollution, lifestyle differences, and divergence in population structure, which may result in differing vulnerability of urban versus rural population to temperature extremes.