Background The World Health Organization considers medication errors to be an issue that requires attention at all levels of care, to reduce the severe and preventable harm related to drug therapy. Different standards for clinical pharmaceutical practices have been proposed by various organizations across the world, where the pharmacist, as part of the multidisciplinary health team, can help improve patient safety. Objective To assess the impact of the introduction of a clinical pharmacy practice model on medication error in patients of a university hospital. Setting The study was conducted in a tertiary care hospital, Medellín, Colombia. Methods A randomized, controlled cluster-wedge staggered trial with a duration of 14 months was conducted to compare the clinical pharmacy practice model with the usual care process in the hospital. Five hospital health care units were included, which were initially assigned to the control group, and after an observation period of 2 months, they were randomly assigned to the intervention group. The trial protocol was registered in ClinicalTrials.gov (identifier NCT03338725). Main outcome measure The incidence of medication errors in hospitalized patients was the main outcome measure. Results The incidence of medication error was 13.3% and 22.8% for the intervention group and control group, respectively. The probability of presenting a medication error was 48% lower when the patient was in the intervention group (RR 0.52; 95% CI: 0.34-0.79). The probability of presenting a medication error over time was 44% lower in the intervention group (p = 0.0005); meanwhile, the resolution of a medication error over time was 70% higher in the intervention group (p = 0. 0029). Conclusion The clinical pharmacy practice model, made up of strategies focused on reducing medication errors, significantly reduces medication errors in patients during hospitalization compared with usual practice. This work assessed the effect of a clinical pharmacy model on the incidence of medication errors and demonstrated its effectiveness in reducing these errors in hospitalized patients. Trial registration ClinicalTrials.gov, NCT03338725. Registered on 9 November 2017. First patient randomized on February 2, 2018.