In this controlled, blinded and randomised study, Circovac®, an inactivated PCV2 vaccine was used for active immunisation of 3-week-old piglets (0.5 ml, i.m., one-shot). In a PCVD affected farm, a total of 1105 piglets from three consecutive farrowing batches were included. The vaccine efficacy was assessed by clinical parameters such as mortality, underweight pigs and improvement of average daily weight gain (ADWG) during the fattening period. Additionally, the effect of the vaccination over time on viremia and seroconversion was investigated in animals from the 1st and the 3rd batch. Mortality rate from start of fattening until slaughter was reduced by 7.40% in the vaccinated group (p < 0.0001). ADWG from 13th to 21st week was improved in the vaccinated group by 64.83 g/day (p < 0.0001) and by 41.43 g/day during the whole fattening stage. Furthermore, vaccination reduced the rate of underweight animals, especially for the obtained weight data in the 21st week of life with 5.15% difference (p = 0.044). The percentage of recently infected animals, characterised by being positive for IgM antibodies, as well as the detection of specific PCV2 DNA, was reduced in the vaccinated animals and it was found concomitant with higher mortality and underweight animals in the non-vaccinated group. From the study results it can be concluded that the vaccination of piglets with Circovac® reduced the viral shedding and protected the animals successfully as shown by the improvement of clinical parameters, and that it can be utilised as a valuable instrument against PCVD.