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<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>