Simple SummaryGenetic variability and recombination of theNSP2gene are of great significance in gaining an in-depth understanding of the prevalence of PRRSV in China over the past 25 years. We compared the nucleotide and amino acid homologies of the NSP2 sequences of different PRRSV-2 lineages, and examined phylogenetic relationships based on an analysis of the NSP2 sequences of 122 strains. What is more, recombination analysis revealed the occurrence of five recombinant events among the 135 selected PRRSV-2 strains. These results provide a theoretical foundation for evolution and epidemiology of the spread of PRRSV.AbstractPorcine reproductive and respiratory syndrome (PRRS) is one of the most serious infectious diseases that detrimentally affects the pig industry worldwide. The disease, which is typically difficult to control, is an immunosuppressive disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV), the genome of which (notably theNSP2gene) undergoes rapid mutation. In this study, we sought to determine the genetic variation in the PRRSV-2NSP2gene in China from 1996 to 2021. Strain information was obtained from the GenBank database and analyzed from a molecular epidemiological perspective. We compared the nucleotide and amino acid homologies of the NSP2 sequences of different PRRSV-2 lineages, and examined phylogenetic relationships based on an analysis of the NSP2 sequences of 122 strains. The results revealed that NADC-30-like strains, which are represented by lineage 1, and HP-PRRSV strains, which are represented by lineage 8, were the most prevalent in China from 1996 to 2021. Close similarities were detected in the genetic evolution of lineages 3, 5, and 8. For nucleotide and amino acid sequence comparisons, we selected representative strains from each lineage, and for the NSP2 among different PRRSV-2 strains, we accordingly detected homologies of 72.5–99.8% and 63.9–99.4% at the nucleotide and amino acid levels, respectively, thereby indicating certain differences in the degrees of NSP2 amino acid and nucleotide variation. Based on amino acid sequence comparisons, we identified deletions, insertions, and substitutions at multiple sites among the NSP2 sequences of PRRSV-2 strains. Recombination analysis revealed the occurrence of five recombinant events among the 135 selected PRRSV-2 strains, and that there is a high probability of recombination of lineage 1 strains. The findings of this study enabled us to gain an in-depth understanding of the prevalence of PRRSV in China over the past 25 years and will contribute to providing a theoretical basis for evolution and epidemiology of the spread of PRRSV.