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Background Haiti has been experiencing a resurgence of diphtheria since December 2014. Little is known about the factors contributing to the spread and persistence of the disease in the country. Geographic information systems (GIS) and spatial analysis were used to characterize the epidemiology of diphtheria in Haiti between December 2014 and June 2021. Methods Data for the study were collected from official and open-source databases. Choropleth maps were developed to understand spatial trends of diphtheria incidence in Haiti at the commune level, the third administrative division of the country. Spatial autocorrelation was assessed using the global Moran’s I. Local indicators of spatial association (LISA) were employed to detect areas with spatial dependence. Ordinary least squares (OLS) and geographically weighted regression (GWR) models were built to identify factors associated with diphtheria incidence. The performance and fit of the models were compared using the adjusted r-squared (R2) and the corrected Akaike information criterion (AICc). Results From December 2014 to June 2021, the average annual incidence of confirmed diphtheria was 0.39 cases per 100,000 (range of annual incidence = 0.04–0.74 per 100,000). During the study period, diphtheria incidence presented weak but significant spatial autocorrelation (I = 0.18, p<0.001). Although diphtheria cases occurred throughout Haiti, nine communes were classified as disease hotspots. In the regression analyses, diphtheria incidence was positively associated with health facility density (number of facilities per 100,000 population) and degree of urbanization (proportion of urban population). Incidence was negatively associated with female literacy. The GWR model considerably improved model performance and fit compared to the OLS model, as indicated by the higher adjusted R2 value (0.28 v 0.15) and lower AICc score (261.97 v 267.13). Conclusion This study demonstrates that GIS and spatial analysis can support the investigation of epidemiological patterns. Furthermore, it shows that diphtheria incidence exhibited spatial variability in Haiti. The disease hotspots and potential risk factors identified in this analysis could provide a basis for future public health interventions aimed at preventing and controlling diphtheria transmission.