Non-typhoidal Salmonella infections are a common cause of gastroenteritis in England. Non-Enteritidis, non-Typhimurium Salmonella serotypes have gained in relative importance in recent years, but their modes of transmission are poorly understood. In a large case-case study in England between 2004 and 2007, the association between exposure to reptiles and Salmonella illness was investigated using multivariable logistic regression. Recent reptile exposure was associated with Salmonella illness with an odds ratio of 2.46 (95% confidence interval: 1.57-3.85, p<0.001), with much stronger effects among children under five years of age. The exposure was rare, and a population attributable fraction was estimated as 0.9%. Among the Salmonella serotypes found in people exposed to reptiles, several non-Enteritidis, non-Typhimurium serotypes were strongly associated with exposure. Reptile exposure is a rare but significant risk factor for Salmonella illness in England, with much higher risk in children.