Trachoma is a major public health concern throughout Ethiopia and other parts of the developing world. Control efforts have largely focused on the antibiotic treatment (A) and surgery (S) components of the World Health Organizations (WHO) SAFE strategy. Although S and A efforts have had a positive impact, this approach may not be sustainable. Consequently, this study focuses on the latter two primary prevention components; facial cleanliness (F) and environmental improvement (E). A geographical approach is employed to gain a better understanding of how culture, economics, environment and behaviour are interacting to determine disease risk in the Kembata Zone of Southern Ethiopia. Specifically, mixed methods were used to investigate what social and environmental factors are influencing the distribution of active trachoma amongst children (aged one to nine) in the Kedida Gamela and Damboya Woredas of the Kembata Zone. The research was completed in collaboration with ORBIS Ethiopia – an NGO providing ophthalmology services - and is a follow up to a baseline trachoma survey conducted in the region. ORBIS Ethiopia provided data on the household trachoma prevalence and the knowledge, aptitude and practices (KAP) of household heads. These data sets were linked in ArcGIS to the geographic coordinates for each household surveyed. Mixed effects logistic regression was used to investigate the strength of a set of fourteen predictor variables in 1) determining whether or not a child a had active trachoma (TF or TI) and 2) determining the level of active trachoma (TF or TI) a child had, given that they had active disease. Younger age, an unclean face and low household expenses were found to be significant risk factors for active trachoma (p < 0.05). Older age and an unclean face were found to be significant risk factors (p < 0.05) for TI, the more severe form, in children with trachoma. Next, the Kulldorff spatial scan statistic was used to identify and map clusters of each risk factor as well as clusters of active disease. The results identified areas of overrepresentation of cases (i.e. active disease, unclean faces, low monthly expenses and low latrine ownership) where the need for intervention is particularly high. Qualitative data from in-depth interviews and focus groups with household heads, teachers and health care professionals were used to identify factors that were encouraging or impeding facial cleanliness and environmental improvement efforts to reduce the spread of trachoma. Lack of food, water and money were identified as important concerns amongst household heads. Based on the interviews with teachers, the study recommends that hygiene education be supported by appropriate access to water in schools. The results of the qualitative and quantitative analyses converged and support continued implementation of the facial cleanliness (F) and environmental improvement (E) components of the WHO’s SAFE strategy.