There is little information on the safety of administration of a third dose of pneumococcal polysaccharide vaccine (PPV). The authors conducted a retrospective assessment of 316,995 adult members of three health maintenance organizations who had received one, two, or three PPV doses. Medical encounters associated with diagnosis codes potentially indicative of an injection site reaction in the week following a first, second, or third PPV dose were identified. These presumptive events occurred in 0.3% (911/279504) of the first PPV group, 0.7% (257/36888) of the second PPV group, and 0.5% (3/603) of the third PPV group (p>0.5 for both comparisons with the third PPV group). These findings do not suggest that a third PPV dose is associated with an increased risk of medically attended injection site reactions compared with a first or second PPV dose.