Vaccination is the best way to prevent economic losses from highly pathogenic porcine reproductive and respiratory syndrome virus (hp-PRRSV) disease. However, the commercially available vaccines need to periodically evaluate their efficacy against infections caused by new hp-PRRSV variants. Therefore, the objective of this study was to evaluate the efficacy of four (two modified live vaccines (MLV) and two inactivated) PRRSV commercial vaccines in piglets challenged with QH-08 and to estimate the genetic distance of the vaccine strains from recently isolated (QH-08) filed strain. Randomly, piglets (n = 5) allocated in groups 1–4 were immunized with Ingelvac PRRS MLV, CH-1a, JXA1, and JXA1-RMLV vaccines, whereas the infected and non-infected control piglets in groups 5 and 6 (n = 3), respectively, were subjected to PBS. Results indicated that JXA1 and JXA1-R MLV vaccines showed complete protection, but Ingelvac PRRS MLV and CH-1α vaccines revealed partial protection against the QH-08 PRRSV challenge. Similarly, vaccinated and challenged pigs showed lower macroscopic and microscopic lesions than the pigs in group 5. Our findings demonstrated a new insight that the variation in ORF1a and 1b coding sequence could significantly affect PRRSV vaccines efficacy. In conclusion, QH-08 is a good candidate for the design and development of an innovative PRRSV vaccine that ultimately helps in the control and prevention strategies.