Background In Switzerland, 20,000 people are hospitalized each year as result of drug related problems (DRPs). The sources of DRPs can be related to patients’ behavior (i.e., wrong administration) or to health processes (i.e., drug-drug interaction). No community pharmacy (CP) service focus on DRPs related to patients’ behavior is currently recognized or remunerated in Switzerland. A medication review with follow up (MRF) has been developed to evaluate prescription and non-prescription medication. Objective To evaluate the impact of MRF service for the identification and management DRPs associated to patients’ behavior and to describe pharmaceutical interventions carried out through MRF. Methods A pre-post intervention study with a cluster design and one intervention group will be carried out in CPs in the canton of Vaud (Switzerland) for 15 months. Volunteer pharmacists will be trained on the identification and management of DRPs related to patients’ behavior. After training, they will include randomly selected adults taking four or more chronic drugs prescribed for at least three months prior to recruitment. Then, they will conduct three pharmacist-patient face-to-face consultations at 6-month intervals. Tasks will be differentiated by pharmacy technician or pharmacist to triage expired medication or to manage DRPs in a structured manner, respectively. The primary outcome is the identification of DRPs associated to patients’ behavior. Secondary outcomes are to assess patients’ medication knowledge, number of expired medications, interventions carried out by pharmacists and pharmacists’ satisfaction. The study will begin in April 2023 in 19 to 35 pharmacies that will recruit at least 162 patients. A sub analysis will be carried out for patients with 65 years old or over. Conclusions The MRF intervention features a training designed for an enhanced evaluation of patient’s behavior towards their medication. The study will allow the assessment and management of DRPs in Swiss CPs with the support of the local health authorities and pharmacist association. Trial registration Clinicaltrials.gov NCT05348538.