Abstract The purpose of this study was the investigation of human leukocyte antigen (HLA) genes in Mexicans with classical Pars Planitis (CPP). Seventy-nine unrelated patients and 204 healthy controls were studied. HLA-A, -B, and -C typing was done on T cells isolated with immunomagnetic beads. HLA-DRB1, -DQA1, and -DQB1 loci were typed by polymerase chain reaction–sequence-specific oligonucleotide probes. The significance and strength of HLA associations were assessed. Stratification analyses were performed to analyze correlations between HLA alleles and clinical manifestations or gender. The mean age of CPP patients was 10 years old. The disease was recurrent (21.3%); 58% were males and 89.6% were bilaterally affected. A 3-year follow-up demonstrated no other associated disease. DRB1*0802 was significantly increased (odds ratio [OR] = 2.8, etiologic fraction [EF] = 18.96%). In females, HLA-B51 (OR = 9.8) was associated with nonsymmetrical onset and HLA-Cw1 (OR = 4.7) with symmetrical onset; DRB1*0802 was increased in males (OR = 3.9, p =5.0 E-05, EF = 38.3%) and contributed to their symmetrical onset (OR = 4.6, p =4.6 E-06, EF = 29.4%). Corneal peripheral endotheliopathy correlated with DQB1*0602 in females (OR = 17, EF = 47.1%). A susceptibility allele of Amerindian ancestry is responsible for juvenile CPP in Mexicans; HLA-B locus contributes to severity in females and DRB1*0802 in males. CPP should be classified as an heterogeneous illness taking into account ethnicity, and clinical and genetic characteristics.