Early protection with a high potency (>6PD50) foot-and-mouth disease (FMD) O1Manisa (Middle-EastSouth Asia lineage) vaccine against challenge with O/VIT/2010 (O Mya98 lineage) was tested in pigs. Onlytwo pigs that were vaccinated seven days prior to challenge had any demonstrable antibodies as a resultof vaccination at the time of challenge. However, 80% and 60% of pigs that were vaccinated seven andfour days prior to coronary band challenge were protected. Vaccination significantly reduced the amountof virus excreted in nasal swabs, saliva and faeces compared to unvaccinated and infected controls. Virusand viral RNA could be detected in some pigs until termination of the experiment 14 days after challenge.Antibodies to the non-structural proteins (NSP) were detected in only one pig that was challenged fourdays post vaccination (dpv) and transiently in two pigs that were challenged seven dpv at only one timepoint. For each vaccine and control group, a group of unvaccinated pigs were kept in the same room butwith no direct contact with the infected pigs to determine whether vaccination prevented transmission.Despite the presence of live virus and viral RNA in these indirect contact pigs, the groups in contact withthe vaccinated and infected pigs did not develop clinical signs nor did they sero-convert. Contact pigs inthe same room as unvaccinated challenged controls did show signs of disease and virus infection thatresulted in sero-conversion to the NSP. A breach of the wall that separated the two groups at nine dayspost challenge might have contributed to this finding. This study showed that high potency vaccine canprovide protection to pigs soon after vaccination and that aerosol transmission within rooms is a rareevent.