Porcine reproductive and respiratory syndrome virus (PRRSV) emerged worldwide approximately 25 years ago, and continues to be the most costly disease of modern swine production. The genetic diversity of PRRSV is one of the major hurdles encountered in attempts to reduce the effects of the virus through vaccines that provide broad cross-protection. The objective of this research is to examine the efficacy of a recently approved vaccine, Fostera^TM PRRS, in growing pigs against separate challenges with heterologous PRRSV strains belonging to lineage 9 and lineage 1. The selected challenge viruses were isolated from recent PRRSV field infections in swine that originated in Iowa. The results of both studies indicate vaccine-induced immunity confers partial protection against the effects of heterologous PRRSV infection, as measured by reduced quantities of virus in serum, oral fluids and bronchoalveolar lavage fluid, and an increase in average daily gain in vaccinated pigs compared to non-vaccinated pigs challenged with the same virus. The two studies resulted in differing levels of protection as measured by severity of lung lesions and quantities of virus in tissues; these differences may be due to several factors, including variations in study design or in the degree of heterogeneity of the challenge viruses. The results show that Fostera^TM PRRS vaccine can provide growing pigs with partial protection against heterologous challenge with currently circulating PRRSV. To improve prevention and control efforts, further investigations are needed into the cross-protection elicited by commercial PRRSV vaccines against contemporary, heterologous virus strains.