OBJECTIVE: To report on strategies for, and outcomes of, evaluation of knowledge (publications), health and wealth (commercial) gains from medical research funded by the Australian Government through the National Health and Medical Research Council (NHMRC). DESIGN AND METHODS: End-of-grant reports submitted by researchers within 6 months of completion of NHMRC funded project grants which terminated in 2003 were used to capture self-reported publication number, health and wealth gains. Self-reported gains were also examined in retrospective surveys of grants completed in 1992 and 1997 and awards primarily supporting people ("people awards") held between 1992 and 2002. RESULTS: The response rate for the 1992 sample was too low for meaningful analysis. The mean number of publications per grant in the basic biomedical, clinical and health services research areas was very similar in 1997 and 2003. The publication output for population health was somewhat higher in the 2003 than in the 1997 analysis. For grants completed in 1997, 24% (31/131) affected clinical practice; 14% (18/131) public health practice; 9% (12/131) health policy; and 41% (54/131) had commercial potential with 20% (26/131) resulting in patents. Most respondents (89%) agreed that NHMRC people awards improved their career prospects. Interpretation is limited by the relatively low response rates (50% or less). CONCLUSIONS: A mechanism has been developed for ongoing assessment of NHMRC funded research. This process will improve accountability to the community and to government, and refine current funding mechanisms to most efficiently deliver health and economic returns for Australia.