The system of medication use (SUM) is composed of multiple processes where nurses, doctors and pharmacy personnel interact, with the former having the most responsibilities. This study sought to establish the prevalence and possible causes of errors in high-risk pharmacological patients in a highly complex hospital. Method: cross-sectional study with follow-up for three months to SUM, with a total of 318 adults; Compliance was reviewed in formulating, delivering, preparing and administering medications. The data were obtained by observation in the field and review of medical records. Results: the overall prevalence of error for every 100 doses / patients throughout the SUM was 5% or more in 95% of cases. Of the total reported errors, 1.89% came to cause harm to the patient. The morning and weekend shifts, the less than six months' experience of the nursing staff and the hospital stay longer than ten days were situations with greater prevalence. Conclusion: the higher prevalence of errors in patients with high pharmacological risk suggests greater difficulty in the management of medications in these cases. Improvement strategies must be aligned with the institutional context and be specific for this group of patients. Abbreviations: SUM, medication use system.