Extreme heat is the leading cause of weather-related mortality in the U.S. Extreme heat also affects human health through heat stress and can exacerbate underlying medical conditions that lead to increased morbidity and mortality. In this study, data on emergency department (ED) visits for heat-related illness (HRI) and other selected diseases were analyzed during three heat events across North Carolina from 2007 to 2011. These heat events were identified based on the issuance and verification of heat products from local National Weather Service forecast offices (i.e. Heat Advisory, Heat Watch, and Excessive Heat Warning). The observed number of ED visits during these events were compared to the expected number of ED visits during several control periods to determine excess morbidity resulting from extreme heat. All recorded diagnoses were analyzed for each ED visit, thereby providing insight into the specific pathophysiological mechanisms and underlying health conditions associated with exposure to extreme heat. The most common form of HRI was heat exhaustion, while the percentage of visits with heat stroke was relatively low (<10%). The elderly (>65 years of age) were at greatest risk for HRI during the early summer heat event (8.9 visits per 100,000), while young and middle age adults (18-44 years of age) were at greatest risk during the mid-summer event (6.3 visits per 100,000). Many of these visits were likely due to work-related exposure. The most vulnerable demographic during the late summer heat event was adolescents (15-17 years of age), which may relate to the timing of organized sports. This demographic also exhibited the highest visit rate for HRI among all three heat events (10.5 visits per 100,000). Significant increases (p < 0.05) in visits with cardiovascular and cerebrovascular diseases were noted during the three heat events (3-8%). The greatest increases were found in visits with hypotension during the late summer event (23%) and sequelae during the early summer event (30%), while decreases were noted for visits with hemorrhagic stroke during the middle and late summer events (13-24%) and for visits with aneurysm during the early summer event (15%). Significant increases were also noted in visits with respiratory diseases (5-7%). The greatest increases in this category were found in visits with pneumonia and influenza (16%), bronchitis and emphysema (12%), and COPD (14%) during the early summer event. Significant increases in visits with nervous system disorders were also found during the early summer event (16%), while increases in visits with diabetes were noted during the mid-summer event (10%).