In recent years, there has been a considerable increase in the use of Modified Live PRRSV Vaccines (MLV) for mass vaccination in Denmark. The potential risks and negative impact of this strategy have been sparsely studied. The aim of this study was to investigate the impact of quarterly sow mass vaccination in two Danish sow herds. The study was performed as an observational prospective cohort of 120 sows in each of two commercial breeding herds in a paired design. Blood samples were taken from sows and oral fluid samples from nursery pigs (four to ten weeks old) before and after vaccination. The presence of PRRSV-1 RNA was measured by real time quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and the level of PRRSV-1 specific antibodies was measured by two different serological assays. PRRS virus was not detected in the sow herds two days before and two weeks after vaccination, but the vaccine strain virus was detected in the nursery pigs. The prevalence of sows without antibodies towards PRRSV-1 went from 6–15% before vaccination to 1–4% after vaccination depending on the serological assay used, despite the fact that they had previously been repeatedly vaccinated. Four sows tested negative for antibodies in both assays after vaccination.