Background: Total antibodies to core antigen of hepatitis B virus (anti-HBc) are a marker for previous or current infection with hepatitis B virus (HBV). Our aim was to examine the prevalence and incidence of anti-HBc in relation to demographic, clinical and laboratory data of patients treated with intermittent hemodialysis (IHD). Methods: Predictors for anti-HBc positivity were evaluated in prevalence IHD patients with negative testing for surface antigen of HBV (HBsAg, n = 1,105) using the stepwise backward regression analysis. Patients starting IHD (n = 336) were introduced into the one-year prospective study evaluating seroconversion for anti-HBc. Results: Anti-HBc positivity (19.5% of all patients) was predicted by lack of vaccination against HBV with developed protective titer of antibodies to HBsAg (β = 0.592, p = 0.000), vintage of renal replacement therapy (RRT, β = 0.206, p = 0.000), history of hepatitis (β = 0.101, p = 0.000), and activity of alanine aminotransferase (β = 0.057, p = 0.037). In 85 prospective patients who finished first IHD year, seroconversion rate for anti-HBc was 1.23 episodes/100 patient-years. Conclusions: Lack of or not effective vaccination against HBV is the strongest predictor for prevalence of anti-HBc positivity in RRT patients. Periodical determination of anti-HBc, usually not required, may be helpful in evaluation of current epidemiological status and risk for further HBV infection in dialysis centers.