BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for persons aged < 65 years with chronic medical conditions. We evaluated the risk and mortality from invasive pneumococcal disease (IPD) among persons with and without the underlying medical conditions which are considered PPV23 indications. METHODS: Population-based data on all episodes of IPD (positive blood or cerebrospinal fluid culture) reported by Finnish clinical microbiology laboratories during 1995-2002 were linked to data in national health care registries and vital statistics to obtain information on the patient's preceding hospitalisations, co-morbidities, and outcome of illness. RESULTS: Overall, 4357 first episodes of IPD were identified in all age groups (average annual incidence, 10.6/100,000). Patients aged 18-49 and 50-64 years accounted for 1282 (29%) and 934 (21%) of IPD cases, of which 372 (29%) and 427 (46%) had a current PPV23 indication, respectively. Overall, 536 (12%) IPD patients died within one month of first positive culture. Persons aged 18-64 years accounted for 254 (47%) of all deaths (case-fatality proportion, 12%). Of those who died 117 (46%) did not have a vaccine indication. In a survival model, patients with alcohol-related diseases, non-haematological malignancies, and those aged 50-64 years were most likely to die. CONCLUSION: In the general population of non-elderly adults, almost two-thirds of IPD and half of fatal cases occurred in persons without a recognised PPV23 indication. Policymakers should consider additional prevention strategies such as lowering the age of universal PPV23 vaccination and introducing routine childhood pneumococcal conjugate immunisation which could provide substantial health benefits to this population through indirect vaccine effects.