Vaccination against the porcine reproductive and respiratory syndrome virus (PRRSv) is widely used to prevent production losses in the swine industry. In this study, piglets born from both PRRSv-vaccinated ELISA-seropositive sows (E+ piglets) and PRRSv-vaccinated ELISA-seronegative sows (E- piglets) were followed-up pre-vaccination, 3 weeks post-vaccination (wpv) and 8 wpv in two Belgian farrow-to-finish herds. The aim of the study was to analyze the presence of PRRSv-specific maternally-derived antibodies (MDAs) and the PRRSv vaccine response in both groups of piglets. The E- piglets lacked the presence of PRRSv-specific MDAs (0% seropositive), while these were present in the E+ piglets (97% seropositive). Due to this, the E- piglets showed a strong initial vaccine response (72-80% seroconversion) and vaccine viremia (65-75% PCR positive) at 3 wpv. In contrast, the E+ piglets showed only limited initial vaccine responses (25-61% with increased ELISA values) and vaccine viremia (30-31% PCR positive) at 3 wpv. By 8 wpv, the proportion of seropositive E- piglets (78-100%) and seropositive E+ piglets (55-90%) increased in both herds. However, a difference in vaccine viremia duration was observed between both herds at 8 wpv, with a decrease in the proportion of PCR positive piglets in herd 1 (E-: 47%; E+: 25%) and an increase in the proportion of PCR positive piglets in herd 2 (E-: 85%; E+: 92%). This study identified clear differences in the presence of PRRSv-specific maternally-derived antibodies and PRRSv vaccine responses between E- and E+ piglets. Further research is warranted to elicit the biological relevance of these observed differences.