BACKGROUND:  The epidemiology of Salmonella Typhi and invasive nontyphoidal Salmonella (NTS) differs, and prevalence of these pathogens among children in sub-Saharan Africa may vary in relation to malaria transmission intensity. METHODS:  We compared the prevalence of bacteremia among febrile pediatric inpatients aged 2 months to 13 years recruited at sites of high and low malaria endemicity in Tanzania. Enrollment at Teule Hospital, the high malaria transmission site, was from June 2006 through May 2007, and at Kilimanjaro Christian Medical Centre (KCMC), the low malaria transmission site, from September 2007 through August 2008. Automated blood culture, malaria microscopy with Giemsa-stained blood films, and human immunodeficiency virus testing were performed. RESULTS:  At Teule, 3639 children were enrolled compared to 467 at KCMC. Smear-positive malaria was detected in 2195 of 3639 (60.3%) children at Teule and 11 of 460 (2.4%) at KCMC (P < .001). Bacteremia was present in 336 of 3639 (9.2%) children at Teule and 20 of 463 (4.3%) at KCMC (P < .001). NTS was isolated in 162 of 3639 (4.5%) children at Teule and 1 of 463 (0.2%) at KCMC (P < .001). Salmonella Typhi was isolated from 11 (0.3%) children at Teule and 6 (1.3%) at KCMC (P = .008). With NTS excluded, the prevalence of bacteremia at Teule was 5.0% and at KCMC 4.1% (P = .391). CONCLUSIONS:  Where malaria transmission was intense, invasive NTS was common and Salmonella Typhi was uncommon, whereas the inverse was observed at a low malaria transmission site. The relationship between these pathogens, the environment, and the host is a compelling area for further research.