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Introduction Residential fires account for the majority of burn-related injuries and fatalities. Established risk factors for burn injury include male gender, racial minority, children and elderly individuals, poverty, and substandard housing characteristics. In North Carolina, the rate of residential fire injuries and deaths is higher than the national average. Therefore, we sought to describe residential fire hospitalizations at a large regional burn center and describe the neighborhoods in which they live. We hypothesized that patients living in areas with higher Area Deprivation Index (ADI) are more likely to have major residential burns. Methods We conducted a retrospective analysis of burn admissions from January 2002 to December 2015. We dichotomized patients into two cohorts: residential and non-residential burns and performed a bivariate analysis. Multivariate Poisson regression models were utilized to determine if ADI was associated with inhalation injury and ≥20% total body surface area burn. Results Of the 10,506 patients presented during the study period. Of these, 10,016 (95.3%) patients resided in North Carolina, and 7894 (78.8%) had a residential burn. Of the overall cohort, 6.0% (n = 458) of patients had ≥20% TBSA burns and 6.4% (n = 506) had inhalation injury. The majority of patients were in the highest (most disadvantaged) ADI quartile (n = 3050, 39.5%), and only 6.8% of patients (n = 525) were in the lowest (least disadvantaged) ADI quartile. In the Poisson multivariate regressions to determine if the ADI was associated with severe burns, patients in the highest ADI quartile had an increased relative risk of ≥20% TBSA burn (RR 1.31, 95% CI 1.02–1.68) and inhalation injury (RR 1.39, 95% CI 1.09–1.76) when compared to patients in the second-lowest ADI quartile when controlled for pertinent covariates. Conclusion Residential structure fires represent the major source of burns and fatalities. People who reside in the highest ADI quartile are more like to present with higher burn injury severity in terms of burn size and the presence of inhalation injury. The use of the ADI to target neighborhoods for burn prevention is imperative.