Drug prescribing for the elderly is an important area of medical knowledge since inappropriate prescribing may lead to significant adverse drug events. The objective of this study was to evaluate the association between knowledge of drug use and quality of drug management by general practitioners in practice. A cross-sectional study design was used to evaluate a sample of 37 GPs in practice. A set of common musculoskeletal problems was chosen to evaluate doctors' knowledge of non-steroidal anti-inflammatory drug use, while performance in practice was assessed using elderly standardized patients. The reliability of knowledge test scores was evaluated using measures of internal consistency. The relationship between knowledge of drug use and quality of therapeutic management in practice was evaluated by rank order and linear correlation analysis. Demographic characteristics of participating and non-participating doctors were similar. The reliability of the knowledge test was 0.55. The reliability of performance scores was 0.66. The correlation between overall performance on the standardized patient cases and total knowledge test score was 0.22 (95% confidence interval = 0-0.63). Knowledge test scores were poorly correlated with quality of therapeutic management in office practice. This indicates that knowledge tests alone cannot predict quality of performance with regard to drug prescribing for the elderly in primary care office practice.