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Purpose: The aim of this study was to examine the risk of being involved in road traffic accidents as drivers among persons using prescribed medicines by utilizing data from population-based registries. The aim of the present paper was to focus on the methodology used in the study. Methods: All Norwegians aged 18-69 in April 2004 to September 2006 (3.1 million), were included in the study. Information on prescriptions, road accidents and emigrations/deaths was obtained from three different population-based registries. A total of 22,000 accidents were observed. The incidence of accidents in exposed and unexposed person-time was compared, by the standardized incidence ratio (SIR). Results: The risk of being involved in an accident was increased in persons exposed for prescribed medicines. The risk was markedly increased in persons exposed for natural opium alkaloids, benzodiazepine tranquillizers, benzodiazepine hypnotics and carisoprodol. A marginal increase or unchanged SIRs were found for NSAIDs, selective beta-2-adrenoreceptor agonists (anti-asthmatics), calcium receptor antagonists and penicillin. Conclusions: We have tested a method using different reference groups and different exposure periods to explore the association between drug use and involvement in traffic accidents. Using these methods, we have shown that exposure for prescribed opiates, benzodiazepines and carisoprodol increased the risk of being involved in an accident as driver. The findings confirm results from other studies. Further steps should be taken to reduce car driving under the influence of these drugs. [ABSTRACT FROM AUTHOR]