Today, medications are manifesting ever more numerous positive clinical effects and have greatly contributed to a lowered mortality rate, prolonged life span and increased quality of life of patients. On the other hand, an increase in unwanted adverse effects of these medications is being marked due to old age, an overabundance of comorbidities and polypharmacy being some of the most important risk factors for the manifestation of the adverse drug reactions (ADRs). Although reporting ADRs is a legal obligation of all healthcare workers, studies show that only around 6 % of ADRs are actually reported. As a consequence, limited data exists on the epidemiology of ADRs. Bearing this in mind, the goal of this research was to determine the frequency of ADRs in a primary care setting and to classify them based on cases of patients that are older than 65 with a diagnosis of hypertension and at least one other underlying cardiovascular disease. An additional goal was to determine the effect of Comprehensive Medication Management (CMM) service on the frequency of ADRs. In the span of two years, a prospective pre-post study on continuously monitored patients that were receiving CMM service was conducted. The frequency of ADRs was analysed based on the sequence number of the patient and their age, sex, number of comorbidities and number of medications taken. The noticed ADRs were classified according to MedDRA (Medical Dictionary for Regulatory Activities) PT (Preferred Term), MedDRA SOC (System Organ Class), occurrence mechanism, seriousness and expectedness. In a total of 65 patients involved in this study, 596 suspicions of ADRs were noted (9,2 ± 16,9 per patient). A strong and statistically notable connection was found between the number of reported ADRs and the number of medications the patient is taking (r = 0,823; p = 0,000). According to MedDRA PT, the leading ADRs were hypotension (42), headache (29) and drug ineffectiveness (27), while according to MedDRA SOC, the leading ADRs were General disorders and administration site conditions (103), Vascular disorders (71) and Gastrointestinal disorders (68). Based on occurrence mechanism, the majority of the total number of reported ADRs was made up of type A ADRs (75 %). Serious and unexpected ADRs represented a lower ratio of the total number of ADRs (12 % and 19 %, respectfully). Additionally, a positive and statistically noticeable effect on the reduction of the frequency of ADRs was observed following the implementation of CMM service (p < 0,001). Taking into consideration both the ever more complex therapy regimens, the increasing number of medications being taken and the increasing number of healthcare workers that can prescribe medications (often without knowing what other healthcare workers have prescribed) and the lack of control over the prescription and consumption of medications, through more careful prescription methods and control of a patient’s therapy, CMM services could serve as a solution to the problem caused by the clinical and financial burden of ADRs, while increasing the efficacy and safety of the use of the prescribed medications.