Background/Objectives: Epitope-based matching has emerged as a refined approach for assessing donor–recipient compatibility in renal transplantation. However, limited data are available on HLA Class I epitope distribution among Indian patients, particularly from northern India, where substantial allelic diversity is known to influence immunological risk. Methods: This retrospective analysis evaluated HLA Class I single-antigen bead (SAB) antibody data from 218 consecutive renal-transplant candidates who tested positive for anti-HLA antibodies between July 2018 and September 2024. HLA Class I epitopes were identified and analyzed using MATCH IT Antibody Software (Immucor, version 1.5.0). Demographic variables and sensitization history (previous transplant, transfusion, pregnancy) were reviewed. Results: A total of 504 distinct epitopes were identified, with 65GK and 163LG emerging as the most frequent motifs. The predominance of these epitopes mirrors the high prevalence of alleles such as HLA-A*24 and HLA-B*35 reported in North-Indian populations. The data suggest a strong influence of regional allele architecture on the immunogenic epitope landscape. Conclusions: This study provides the first baseline characterization of HLA Class I epitope distribution among northern-Indian renal-transplant candidates. The findings emphasize the need for establishing population-specific HLA epitope databases and highlight the potential of epitope-based matching to enhance donor selection and minimize immunological risk in Indian transplantation programs.