To predict which patients with current high-risk disease in the community may benefit most from additional preventive or therapeutic measures for influenza, we determined prognostic factors for influenza-associated hospitalization and death in a general practice-based case-control study among this segment of the vaccine target population with high influenza vaccination rates. In 103 general practices followed during the 1996/7 influenza epidemic, cases were either hospitalized, or died due to influenza, bronchitis, pneumonia, diabetes, heart failure or myocardial infarction. Age- and gender-matched controls were randomly sampled from the remaining cohort. Information was collected by review of patient records. In total, 119 cases and 196 matched controls were included. Of the cases, 34, 25 and 4% were hospitalized for acute pulmonary and cardiac disease and diabetes, respectively, and 37% died. Multivariate conditional logistic regression analysis revealed that presence of chronic obstructive pulmonary disease, heart failure, previous hospitalization, high GP visiting rate and polypharmacy were independent prognostic factors. Several non-modifiable determinants can be used to ensure targeting additional preventive or therapeutic measures at the most vulnerable segment of the vaccine target group.