Patients with chronic diseases are at increased risk of complications following infection. It remains, however, unknown to what extend they are protected against vaccine-preventable diseases. We assessed seroprevalence of antibodies against diphtheria, tetanus and pertussis to evaluate whether current vaccination programs in Belgium are adequate. Antibody titers were assessed with a bead-based multiplex assay in serum of 1052 adults with chronic diseases. We included patients with diabetes mellitus type 1 (DM1) ( = 172), DM2 ( = 77), chronic kidney disease ( = 130), chronic obstructive pulmonary disease (COPD) ( = 170), heart failure ( = 77), HIV ( = 196) and solid organ transplant (SOT) recipients ( = 230). Factors associated with seroprevalence were analysed with multiple logistic regression. We found seroprotective titers in 29% for diphtheria (≥0.1 IU/mL), in 83% for tetanus (≥0.1 IU/mL) and 22% had antibodies against pertussis (≥5 IU/mL). Seroprotection rates were higher ( < 0.001) when vaccinated within the last ten years. Furthermore, diphtheria seroprotection decreased with age ( < 0.001). Tetanus seroprotection was less reached in women ( < 0.001) and older age groups ( < 0.001). For pertussis, women had more often a titer suggestive of a recent infection or vaccination (≥100 IU/mL, < 0.01). We conclude that except for tetanus, the vast majority of at-risk patients remains susceptible to vaccine-preventable diseases such as diphtheria and pertussis.