Since 1996 Salmonella Typhimurium DT104 salmonellosis has increased in The Netherlands. This prompted a case-control study of risk factors for salmonellosis to inform transmission routes for this phage type. Cases were laboratory-confirmed patients with a Salmonella infection and controls were selected from population registries by frequency matching for age, sex, degree of urbanization and season. Cases and controls received a questionnaire on risk factors. Of the 1171 cases, 573 (49%) responded: 245 S. Enteritidis and 232 S. Typhimurium cases (both DT104 and non-DT104), of which 58 were DT104. Of the 10250 controls, 3409 (33%) responded. Use of H2 antagonists [odds ratio (OR) 4·4, 95% CI 1·6–12·2] and proton pump inhibitors (OR 4·2, 95% CI 2·2–7·9), consumption of raw eggs (OR 3·1, 95% CI 1·3–7·4) and products containing raw eggs (OR 1·8, 95% CI 1·1–3·0) were associated with endemic S. Enteritidis infection. Risk factors for endemic S. Typhimurium infection were use of proton pump inhibitors (OR 8·3, 95% CI 4·3–15·9), occupational exposure to raw meat (OR 3·0, 95% CI 1·1–7·9), playing in a sandbox (for children aged 4–12 years) (OR 2·4, 95% CI 1·6–3·7), consumption of undercooked meat (OR 2·2, 95% CI 1·1–4·1) and use of antibiotics (OR 1·9, 95% CI 1·0–3·4). Use of proton pump inhibitors (OR 11·2, 95% CI 3·9–31·9) and playing in a sandbox (OR 4·4, 95% CI 1·8–10·7) were the only risk factors for S. Typhimurium DT104 salmonellosis. This study confirms known risk factors for salmonellosis. However, playing in a sandbox was a predominant new risk factor for S. Typhimurium salmonellosis in children [population attributable risk (PAR) 14%], and especially for S. Typhimurium DT104 (PAR 32%).