Despite implementing preventive measures, mastitis caused by Staphylococcus aureus remains a significant challenge in Swedish dairy farming, and an efficient vaccine against mastitis is still sought. In this research article, results from a clinical trial evaluating the efficacy of a novel experimental vaccine against S. aureus-induced mastitis in a Swedish dairy herd with continuous calving are presented. The vaccine was formulated with NanoQuil adjuvant and formalin-fixed S. aureus antigen. The trial was conducted as a comparative study in which previously unvaccinated cows were vaccinated before calving with either the experimental vaccine or a commercially available control vaccine (Startvac). Milk yield and somatic cell count (SCC) were the primary evaluation criteria. Data from the Swedish Official Milk Recording Scheme were used in the analysis of infection rates and herd udder health. In total, data from 144 cows across 199 lactation periods were evaluated. The two vaccine groups did not exhibit any significant differences in milk yield, and there were only minor, inconsistent differences in SCC between the treatments. However, the overall herd udder health evidently improved after the introduction of the control and treatment vaccines. No difference in the rate of new infections, as indicated by SCC increases above a threshold of 150 000 cells/ml between samplings, was recorded between the experimental groups. In contrast, the rate of new infections during the dry period tended to be lower. The recovery rate tended to be higher for cows vaccinated with the experimental vaccine, although not statistically significant.