Abstract Background In Belgium, the debate about the effect of the national academic detailing service (ADS) on prescribing quality in general practice is ongoing. In order to evaluate both the implementation strategies of the ADS and its effectiveness on appropriate prescribing of pain relief medication, we conducted a real-world cluster randomized controlled trial (cRCT). Methods In a pragmatic cRCT, all Belgian general practices previously visited by Farmaka were assessed for eligibility and randomized. Only practices randomized to the intervention group were invited for an academic detailing visit on appropriate prescribing of pain relief medication. GPs were unaware of the study, ensuring the production of real-world evidence but were given the option to opt out from the analysis. An objective outcome assessment was obtained using routinely collected reimbursement data. Primary outcomes were the proportion of patients reimbursed for an analgesic or NSAID, the defined daily dose of paracetamol per ...