INTRODUCTION    Hemodialysis (HD) patients show a weaker response to hepatitis B virus (HBV) vaccination than the healthy population. Several gene variants were reported to be associated with the levels of antibodies to HBV surface antigen (anti‑HBs) after HBV vaccination among healthy individuals. OBJECTIVES    The aim of the study was to determine the effect of immunity‑related genes on the maximum anti‑HBs antibody levels after vaccination among HD subjects. PATIENTS AND METHODS    This 6‑year prospective study included HD patients who were not infected with HBV and underwent HBV vaccination. Before the study, patients were classified as responders (anti‑HBs ≥10 IU/l, n = 356) or nonresponders (anti‑HBs <10 IU/l, n = 48) to HBV vaccination. Patients were tested for the following gene variants: GC rs7041, rs1155563, rs2298849; RXRA rs10881578, rs10776909, rs749759; VDR rs1544410, rs2228570; IFNL3 rs8099917, rs12979860; IL12A rs568408; IL12B r3212227; IL4R rs1805015; IL13 rs20541; IL18 rs360719; and CCL2 rs1024611. Anti‑HBs titers were checked every 6 to 12 months and the individual maximum values were used in the analysis. RESULTS    There was a significant difference in peak anti‑HBs levels between patients with 2 major alleles of IL12A rs568408 (median, 180 IU/l; range, 0–4.105 IU/l) and those carrying 1 or 2 minor alleles (median, 451 IU/l; range, 0–5.342 IU/l; P = 0.004). In a multivariate analysis, a positive correlate of the maximum anti‑HBs antibody titers was dialysis duration, while the negative ones included the GG genotype of IL12A rs568408, age, and time elapsed from dialysis onset to peak anti‑HBs antibody titers. CONCLUSIONS    In HD patients, peak anti‑HBs levels following vaccination are independently associated with the IL12A rs568408 variant.