In Baden-Wuerttemberg, a federal state in south-west Germany, a large outbreak of 1089 laboratory-confirmed human Puumala virus (PUUV) infections occurred in 2007. We conducted a survey to describe the disease burden and a case-control study to identify risk factors for acquiring PUUV. Case-patients were interviewed about clinical outcome and both case-patients and randomly recruited controls were interviewed about exposure. We calculated matched odds ratios (mOR) using a conditional logistic regression model. Multivariable analysis of 191 matched case-control pairs showed that case-patients were more likely than controls to have seen small rodents/their droppings (mOR 1.9, 95% CI 1.2-3.0), cleaned utility rooms (mOR 1.8, 95% CI 1.0-3.4) and visited forest shelters (mOR 3.9, 95% CI 1.1-14.3). Two thirds of case-patients required hospitalization. During PUUV epidemics rodent control measures and use of protective equipment should be considered in utility rooms and shelters.