Patients with chronic kidney disease (CKD) or on dialysis are at greater risk of infection, which might be due to a defective immune function. While there are controversial reports on efficacy of vaccination in this group of patients, the aim of this study was to evaluate the antibody response to pneumococcal capsular polysaccharide vaccine (PPV23) in CKD patients. Sixty-six patients with CKD and 40 healthy individuals were vaccinated with PPV23. Blood samples were taken before and four weeks after vaccination. Specific antibodies against whole pneumococcal antigens were measured using an enzyme-linked immunosorbent assay (ELISA) technique. Among the 66 vaccinated patients, 14 (21%) were hypo-responsive to vaccine (group 1), while 52 had a normal specific-antibody response (group 2). Post-vaccination, anti-pneumococcal IgG titers in group 1 were significantly lower than those in group 2 (p = 0.012 for IgG post-vaccination and p = 0.020 for IgG2 post-vaccination). The fold increase or ratio increase of the anti-pneumococcal IgG titer in patients of group 1 was also significantly lower than that in group 2 or the healthy control group (p = 0.001 versus group 2 and p = 0.005 versus control group). During follow-up of both patient groups, group 1 patients developed more episodes of pneumococcal infections than those patients in group 2 (p = 0.007). In conclusion, although the majority of patients with CKD were responders to the polysaccharide vaccine, a substantial proportion of patients failed to mount an adequate antibody response to PPV23 and remained at significant risk of pneumococcal infection. Nevertheless, this vaccination policy should be administered as it could prevent infection in responder patients.