The population of developed countries is aging, leading to an increase in the use of medication in daily practice, which can lead to serious treatment costs and irrational polypharmacy. A collaborative care approach, such as providing medication review service provided by a clinical pharmacist (CP), is a possible way to reduce drug-related problems and irrational polypharmacy. The aim of this study was to determinate whether a CP's medication review service can improve the quality of drug prescribing in elderly patients treated with polypharmacy in primary care. In a retrospective observational medical chart review study, patients aged 65 years or more in the period 2012-2014 who received 10 or more medications concomitantly and who were screened by a CP were included. Data on pharmacotherapy and CPs' interventions were obtained from the patients' medical records (non-electronic chart review). Potential drug-drug interactions (pDDIs) were determined with Lexicomp Online™ 3.0.2. Only potential X-type DDIs (pXDDIs) were included. Potentially inappropriate medications in the elderly (PIMs) were identified using the PRICUS list. Ninety-one patients were included. The CPs suggested 625 interventions, of which 304 (48.6%) were accepted by the general practitioners (GPs). After adopting the CPs' interventions, the number of total medications decreased by 11.2% (p <  0.05) and the number of pXDDIs decreased by 42% (p <  0.05). The number of clinically important pXDDIs decreased by 50% (3 cases). The number of prescribed PIMs decreased by 20% (p = 0.069). The acceptance of CP's recommendations reduced the number of pXDDIs (p < 0.05) and improved the adherence to heart failure treatment guidelines. A collaborative care approach offering a CP medication review service significantly improved the quality of pharmacotherapy by reducing the total number of medications and pXDDIs. The results support the implementation of this service in the Slovenian healthcare system.