Several recent studies have assessed the benefits of extending influenza vaccination programmes, which are currently targeted primarily at those aged over 65 years, to those aged 50–64 years. We identified and reviewed all cost-effectiveness studies of influenza vaccination in those aged 50–64 years published before July 2008. While the studies suggest that vaccination in this age-group is likely to be cost effective, these results were dependent on several key assumptions. The estimates of serious outcomes due to influenza and the estimates of vaccine effectiveness (VE) against these outcomes were found to have the most influence on cost effectiveness. However, due to factors including mismatches between the measure of VE and the outcome under consideration, as well as various other data limitations, there is significant uncertainty around these key assumptions that was not well explored. There was a failure in some studies to report fundamental inputs such as discount rates. Overall, there was a general lack of transparency in the studies and, consequently, the conclusions around the cost effectiveness of influenza vaccine in those aged 50–64 years must be interpreted with caution.