The objective of this study was to assess the effect of concurrent infection with porcine reproductive and respiratory syndrome virus (PRRSV) on the efficacy of an inactivated swine influenza virus (SIV) vaccine. Eight groups of pigs were infected with a virulent PRRSV isolate either between the two SIV vaccines or at the time of SIV challenge. Control groups included SIV vaccination without PRRSV and pigs infected with SIV and/or PRRSV. Pigs infected with PRRSV during vaccination showed increased levels of macroscopic and microscopic lesions compared to pigs vaccinated against and challenged with only SIV indicating decreased SIV vaccine efficacy. In addition, pigs vaccinated in the presence of PRRSV showed increased clinical disease and shedding of SIV during the acute phase of SIV infection. No alterations in the systemic or local antibody response to either SIV vaccination or challenge were observed. These findings demonstrate that PRRSV infection has a significant impact on SIV vaccine efficacy that may be important for disease control.