Background: Cardiovascular health effects of fine particulate matter (PM2.5) exposure from wildfire smoke are neither definitive nor consistent with PM2.5 from other air pollution sources. Non-comparability among wildfire health studies limits research conclusions. Methods: We examined cardiovascular and respiratory health outcomes related to peat wildfire smoke exposure in a population where strong associations were previously reported for the 2008 Evans Road peat wildfire. We conducted a population-based epidemiologic investigation of associations between daily county-level modeled wildfire PM2.5 and cardiopulmonary emergency department (ED) visits during the 2011 Pains Bay wildfire in eastern North Carolina. We estimated changes in the relative risk cumulative over 0–2 lagged days of wildfire PM2.5 exposure using a quasi-Poisson regression model adjusted for weather, weekends, and poverty. Results: Relative risk associated with a 10 μg/m3 increase in 24-h PM2.5 was significantly elevated in adults for respiratory/other chest symptoms 1.06 (1.00–1.13), upper respiratory infections 1.13 (1.05–1.22), hypertension 1.05 (1.00–1.09) and ‘all-cause’ cardiac outcomes 1.06 (1.00–1.13) and in youth for respiratory/other chest symptoms 1.18 (1.06–1.33), upper respiratory infections 1.14 (1.04–1.24) and ‘all-cause’ respiratory conditions 1.09 (1.01–1.17). Conclusions: Our results replicate evidence for increased risk of cardiovascular outcomes from wildfire PM2.5 and suggest that cardiovascular health should be considered when evaluating the public health burden of wildfire smoke.