The objectives of this study were to estimate the incidence of salmonellosis among a large sample of dairy herds in the northeastern United States (both at the animal level and the herd level), to describe the serotypes and antimicrobial resistance profiles of the positive samples, and to determine whether various herd-level factors were important predictors of incidence. Participating veterinarians enrolled 831 dairy herds and submitted fecal samples from 2,565 female dairy cattle for Salmonella culture because of suspicion of clinical disease. Estimates of animal-level incidence rates were calculated for each age group as the number of cases per animal time at risk, and an estimate of herd-level incidence rate was calculated as the number of positive herds per herd time at risk. Descriptive analysis of serotype data and level of antimicrobial resistance was performed, and Poisson regression analysis was used to study associations between the within-herd incidence of salmonellosis and certain predictor variables (herd size, housing type, vaccination status, and prior history of Salmonella infection). Salmonella was isolated from 576 (22.5%) samples representing 93 herds. The animal-level incidence rates for preweaned female calves, heifers, and adult cows were 8.1, 0.04, and 1.8 cases per 1,000 animal-years, respectively. The herd-level incidence rate was 8.6 positive herds per 100 herd-years. Salmonella Newport was the predominant serotype, accounting for 41% of the cases, followed by Salmonella Typhimurium. Over 68% of all isolates were resistant to 5 or more antimicrobial agents. Herd size was the only significant predictor of the incidence of salmonellosis in a multivariable model; herds with at least 400 female dairy cattle had a higher incidence rate than smaller herds. Our results shed light on the impact of salmonellosis on the dairy industry in the northeastern United States, and they help clarify the role of dairy cattle as a source of Salmonella serotypes that are also important human pathogens.