We assessed malaria infection in relation to age, altitude, rainfall, socio-economic factors and coverage of control measures in a representative sample of 11437 people in Amhara, Oromia and SNNP regions of Ethiopia in December 2006-January 2007. Surveys were conducted in 224 randomly selected clusters of 25 households (overall sample of 27884 people in 5708 households). In 11538 blood slides examined from alternate households (83% of those eligible), malaria prevalence in people of all ages was 4.1% (95% CI 3.4-4.9), with 56.5% of infections being Plasmodium falciparum. At least one mosquito net or one long-lasting insecticidal net (LLIN) was present in 37.0% (95% CI 31.1-43.3) and 19.6% (95% CI 15.5-24.5) of households, respectively. In multivariate analysis (n=11437; 82% of those eligible), significant protective factors were: number of LLINs per household (odds ratio [OR] (per additional net)=0.60; 95% CI 0.40-0.89), living at higher altitude (OR (per 100 m)=0.95; 95% CI 0.90-1.00) and household wealth (OR (per unit increase in asset index)=0.79; 95% CI 0.66-0.94). Malaria prevalence was positively associated with peak monthly rainfall in the year before the survey (OR (per additional 10 mm rain)=1.10; 95% CI 1.03-1.18). People living above 2000 m and people of all ages are still at significant risk of malaria infection.