Background. Malaria is a major public health burden in the south-eastern part of Bangladesh, particularly in the Chittagong Hill Tracts region. In 2007, BRAC and ICDDR,B carried out a malaria prevalence survey in the endemic regions including the Khagrachari District. Methods. This study was done to detect clusters of malaria and identify the geographic risk factors. Thirty mauzas (the lowest administrative unit/bigger than village in Bangladesh that has polygon boundary) from the area were selected for the survey using probability proportional to size (PPS) sampling. Twenty-five households within each mauza were then randomly selected for screening, with a GPS point being recorded at each household. Rapid diagnostic tests were used to diagnose malaria. Results. The average malaria prevalence in the District was 15.47% (n = 750). SaTScan detected five geographic clusters of malaria, one of which was highly significant (p = 0.001). Malaria cases were significantly associated with proximity to water bodies and forests. Conclusion. The data presented in this paper are the first step to understanding malaria in southeastern Bangladesh from a micro-geographic perspective. The study results suggest that there are 'malaria hot-spots' in the study area. The government of Bangladesh and non-governmental organizations involved in malaria control should consider these results when planning malaria control measures. In particular, malaria maps should be updated on a regular basis as new data become available.