Background Knowledge of drug-related problems (DRPs) identified in the medication of home-dwelling elderly patients with polypharmacy has been based predominantly on medication reviews conducted in research settings rather than in daily practice. Objective To evaluate the prevalence of DRPs identified by means of a clinical medication review (CMR) and the implementation rate of proposed interventions in a large group of older patients with polypharmacy in the daily practice of community pharmacies. Setting 318 Dutch community pharmacies. Method A cross-sectional study based on CMR-data of 3807 older patients (≥65 years) with polypharmacy (≥5 drugs) completed between January and August 2012. Data were extracted from community pharmacists’ databases and entailed: year of birth, gender, dispensing data, number and nature of identified DRPs, consultations performed, proposed and implemented interventions. Main outcome measure Prevalence of DRPs, drug classes involved in overtreatment and undertreatment, and proposed and implemented interventions. Results A median of two DRPs (interquartile range 1–4; mean 3.0) was identified per patient. The DRP-categories overtreatment (25.5 %) and undertreatment (15.9 %) were found most frequently. 46.2 % of the proposed interventions to solve DRPs were implemented as proposed, in 22.4 % of cases, the intervention differed from the proposal. In 31.3 % of cases no intervention was implemented. Conclusion By conducting a CMR community pharmacists identified a median of two DRPs in older patients with polypharmacy. Overtreatment and undertreatment accounted for 41.4 % of the DRPs identified. In dealing with DRPs, pharmacists proposed a variety of interventions of which the majority (69.9 %) was either implemented or led to alternative interventions. A set of explicit criteria should be applied during a CMR to solve and prevent DRPs.