BACKGROUND: Older patients tend to have multimorbidity, represented by multiple chronic diseases or geriatric conditions, which leads to a growing number of prescribed medications. As a result, pharmacological prescription has become a major concern because of the increased difficulties to ensure appropriate prescription in older adults. The study's main objectives were to characterize a cohort of older adults with multimorbidity, carry out a medication review and compare the pharmacological data before and after the medication review globally and according to the frailty index. METHODS: This was a quasi-experimental (uncontrolled pre-post) study with a cohort of patients ≥ 65 years old with multimorbidity. Data were collected from June 2019 to October 2020. Variables assessed included demographic, clinical, and pharmacological data, degree of frailty (Frail-VIG index), medication regimen complexity index, anticholinergic and or sedative burden index, and monthly drug expenditure. Finally, a medication review was carried out by an interdisciplinary team (primary care team and a consultant team with a geriatrician and a clinical pharmacist) by applying the Patient-Centered Prescription model to align the treatment with care goals. RESULTS: Four hundred twenty-eight patients were recruited [66.6% women; mean age 85.5 (SD 7.67)]. The mean frail index was 0.39 (SD 0.13), corresponding with moderate frailty. Up to 90% of patients presented at least one inappropriate prescription, and the mean of inappropriate prescriptions per patient was 3.14 (SD 2.27). At the three-month follow-up [mortality of 17.7% (n = 76)], the mean chronic medications per patient decreased by 17.96%, varying from 8.13 (SD 3.87) to 6.67 (SD 3.72) (p < 0.001). The medication regimen complexity index decreased by 19.03%, from 31.0 (SD 16.2) to 25.1 (SD 15.1), and the drug burden index mean decreased by 8.40%, from 1.19 (SD 0.82) to 1.09 (SD 0.82) (p < 0.001). A decrease in polypharmacy, medication regimen complexity index, and drug burden index was more frequent among frail patients, especially those with severe frailty (p < 0.001). CONCLUSIONS: An individualized medication review in frail older patients, applying the Patient-Centered Prescription model, decreases pharmacological parameters related to adverse drug effects, such as polypharmacy, therapeutical complexity, and anticholinergic and, or sedative burden. The benefits are for patients with frailty.