Diphtheria is of great epidemiological concern. Although mainly observed during childhood, unvaccinated adults and relatively immunocompromised patients are at increased risk for acquiring diphtheria. We aimed to determine the rates and certain determinants of protection against diphtheria in adult hemodialysis (HD) patients. Protection rates of 322 HD patients were compared with 65 diabetes mellitus type 2 (DM) patients and 65 healthy controls. A questionnaire was held in regard to smoking habits and alcohol intake. Antibody levels against diphtheria were assessed by an in-house ELISA and a concentration of >= 0.1 IU/mL was regarded as protective. Effects of age, gender and time being on dialysis on protection were assessed by logistic regression. Ratios of individuals with protective antibody levels were found to be 36% (116/322), 27.7% (18/65), and 52.3% (34/ 65) for HD, DM, and control groups, respectively. Hemodialysis patients had a significantly (p < 0.05) lower protection rate than healthy controls. In all study groups, there was a tendency of higher protection rate with increasing age. These low ratios of protected individuals in both HD and DM patient groups are alarming, as these patients generally have defects in vaccine responses, and carriage is important in the perpetuation of diphtheria. The protection status of these patient groups might be improved with additional vaccinations.