To identify risk factors for sporadic Salmonella Typhimurium definitive phage-type 104 (DT104) and non-DT104 diarrhoeal illness in Canada, we conducted a matched case-control study between 1999 and 2000. Cases were matched 1[ratio ]1 on age and province of residence. Multivariate analysis suggested that recent antibiotic use [odds ratio (OR) 5·2, 95% confidence interval (CI) 1·8–15·3], living on a livestock farm (OR 4·9, 95% CI 1·9–18·9), and recent travel outside Canada (OR 4·1, 95% CI 1·2–13·8) are independent risk factors for DT104 illness. Similar analyses suggested that recent travel outside North America is a sizable risk factor for non-DT104 illness (OR 66·8, 95% CI 6·7–665·3). No food exposure was a risk factor in either analysis. Educating health-care providers and the public about appropriate antibiotic use and antimicrobial resistance is important. Appropriate administration of antibiotics to livestock, particularly cattle, and hygienic measures such as handwashing after contact with farm animals may reduce risk. Travel represents an important and probably underestimated risk factor for sporadic illness with S. Typhimurium. Improved national surveillance and detailed investigation of travel-related illness are required.