Pneumococcal vaccination among the elderly is currently recommended in several western countries. We estimated the cost-effectiveness of a hypothetical vaccination campaign of 65+ year olds in the Lazio region (Italy). Baseline net costs per event averted and life-year gained, at 2001 prices, were euro 34,681 (95%CI: euro 28,699 to euro 42,929) and euro 23,361, respectively (95%CI: euro 16,419 to euro 38,297). Lower bacteraemic pneumonia incidence and vaccine effectiveness increased the net cost per life-year gained (ICER) to euro 53,899 and euro 74,313, respectively; in the best-case scenario the ICER was euro 4249. The case definition of invasive pneumococcal disease and, consequently, vaccine effectiveness are major uncertainties in countries with low incidence of pneumonia.