Background Around 20-30% of all prescribed drugs are estimated to be metabolised by the cytochrome P450 (CYP) 2D6 enzyme. In a medical practice, it is usually not known whether a patient is a poor, intermediate, normal or ultra-rapid metaboliser for CYP2D6-metabolised drugs. Objective This study aims to explore the clinical relevance and the extent of hazardous prescriptions by analysing the metaboliser status of patients already taking such drugs. Methods This is a family practice-based observational study performed in a rural practice for general and family medicine in Lower Austria providing care for approximately 2100 patients annually. In 287 consecutive patients, who had taken or were taking a drug metabolised by CYP2D6 during the last 3 years, the metaboliser status was analysed. Results The genetic analysis of 287 patients resulted in 51.22% normal metabolisers, 38.68% intermediate metabolisers, 6.27% poor metabolisers and 3.83% ultra-rapid metabolisers. In 50 cases (poor metaboliser, intermediate metaboliser and ultra-rapid metaboliser, i.e. 17.42% of all tested patients taking a CYP2D6-specific drug), an altered gene function was identified, for which clinical guideline annotations, drug label annotations, or clinical annotations are available. Allele and genotype frequencies were in accordance with data from other European studies. Conclusions In 17.42% of all patients already taking a drug metabolised by CYP2D6, knowledge of the genetically defined metaboliser status would have been of immediate clinical relevance before prescribing the drug. ClinicalTrials.gov identifier NCT03859622.