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<p>Abstract</p> <p>Background</p> <p>Malaria due to <it>Plasmodium falciparum </it>is the leading cause of morbidity and mortality in Tanzania. According to health statistics, malaria accounts for about 30% and 15% of hospital admissions and deaths, respectively. The risk of <it>P. falciparum </it>infection varies across the country. This study describes the spatial variation and socio-economic determinants of <it>P. falciparum </it>infection in northeastern Tanzania.</p> <p>Methods</p> <p>The study was conducted in 14 villages located in highland, lowland and urban areas of Korogwe district. Four cross-sectional malaria surveys involving individuals aged 0-19 years were conducted during short (Nov-Dec) and long (May-Jun) rainy seasons from November 2005 to June 2007. Household socio-economic status (SES) data were collected between Jan-April 2006 and household's geographical positions were collected using hand-held geographical positioning system (GPS) unit. The effects of risk factors were determined using generalized estimating equation and spatial risk of <it>P. falciparum </it>infection was modelled using a kernel (non-parametric) method.</p> <p>Results</p> <p>There was a significant spatial variation of <it>P. falciparum </it>infection, and urban areas were at lower risk. Adjusting for covariates, high risk of <it>P. falciparum </it>infection was identified in rural areas of lowland and highland. Bed net coverage levels were independently associated with reduced risk of <it>P. falciparum </it>by 19.1% (95%CI: 8.9-28.2, p < 0.001) and by 39.3% (95%CI: 28.9-48.2, p < 0.001) in households with low and high coverage, respectively, compared to those without bed nets. Households with moderate and lower SES had risk of infection higher than 60% compared to those with higher SES; while inhabitants of houses built of mud walls were at 15.5% (95%CI: 0.1 - 33.3, p < 0.048) higher risk compared to those living in houses built by bricks. Individuals in houses with thatched roof had an excess risk of 17.3% (95%CI: 4.1 - 32.2, p < 0.009) compared to those living in houses roofed with iron sheet.</p> <p>Conclusions</p> <p>There was high spatial variation of risk of <it>P. falciparum </it>infection and urban area was at the lowest risk. High bed net coverage, better SES and good housing were among the important risk factors associated with low risk of <it>P. falciparum </it>infection.</p>