The pneumococcal surface protein PspA, a cell-wall-associated surface protein, is a promising component for pneumococcal vaccines. In this study, the distribution of the PspA family was determined in a panel of invasive and clinically important pneumococcal isolates from adults over 50 years of age, collected between 1995 and 2002. One thousand eight hundred and forty-seven recent isolates from invasive pneumococcal disease were obtained from seven Western countries, together with clinical data. An ELISA-based serological method was standardized in order to determine the PspA family and clade distribution. Molecular tests were used when isolates were non-typable by ELISA (PspA family typing by PCR). Only 42 (2.3%) isolates were non-typable by ELISA and PspA family typing by PCR was performed. Finally, 3 isolates were considered as non-pneumococcal and 1844 were classified as follows: 749 (40.6%) were PspA family 1, 1078(58.5%) were PspA family 2, 13 (0.7%) were PspA family 1 and 2 and 4(0.2%) remained non-typable. The cross-reactivity of antibodies to PspAs of different clades was confirmed. In conclusion, inclusion of PspA family 1 and family 2 in future pneumococcal vaccines would ensure broad coverage of pneumococcal strains infecting people over 50 years of age. © 2006 SGM.