Malaria is endemic to Bangladesh. In this longitudinal study, we used hydrologic, topographic, and socioeconomic risk factors to explain single and multiple malaria infections at individual and household levels. Malaria incidence was determined for 1,634 households in 54 villages in 2009 and 2010. During the entire study period 21.8% of households accounted for all (n = 497) malaria cases detected; 15.4% of households had 1 case and 6.4% had ≥ 2 cases. The greatest risk factors for malaria infection were low bed net ratio per household, house construction materials (wall), and high density of houses. Hydrologic and topographic factors were not significantly associated with malaria risk. This study identifies stable malaria hotspots and risk factors that should be considered for cost-effective targeting of malaria interventions that may contribute to potential elimination of malaria in Bangladesh.