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.