La Crosse encephalitis (LACE) is the most commonly reported mosquito-borne illness in North Carolina, and the annual incidence of LACE in NC is among the highest in the nation--North Carolina accounts for 25% of all LACE cases reported to the Centers for Disease Control and Prevention (CDC) from 2008-2012. Within North Carolina, LACE is reported from western NC, with 7 mountain counties in the southwestern portion of the state accounting for over 90% of all cases in NC since 2000. LACE is commonly found in rural, wooded areas, where peridomestic environments are conducive to mosquito exposure, but few epidemiologic studies have quantified the association between peridomestic habitat and LACE. Using a cohort of 501 patients tested for arboviral disease at MHS, the risk of LACE was compared based on demographic and peridomestic risk factors including age, gender, rural residence, peridomestic land cover, type of home, and number of objects around the home. Of the 69 cases, the majority were white, non-Hispanic, and under the age of 16 with clinically measured fever, headache, vomiting, and altered mental status. Upon adjustment for age, the risk of LACE among those living in forested rural areas was 2.55 times the risk among those living in non-forested or urban areas (95% confidence interval: 1.59, 4.09). Confirmed and probable cases of LACE in NC, identified from historical reportable disease surveillance data from 2000-2012, were aggregated at the county and census tract-level to determine the extent and location of spatial clusters of LACE cases. Spatial scan statistics generated from unadjusted and covariate-adjusted models detected 4 clusters of high LACE incidence throughout western NC. The clusters identified in this study occur at the sub-county level, and may not have been identified using traditional county-level analyses. The results of this research identify peridomestic risk factors for LACE at the individual level and identify locations of high LACE incidence throughout western NC. These investigations contribute to the general knowledge of LACE and allow for targeted public health interventions to reduce the future occurrence of LACE in western NC.