Purpose: This study aims to identify and compare the relevance of barriers that nurses in nursing homes experience in medication management in Belgium. Design: The mixed-method study started with an expert meeting in November 2008 and was followed by a cross-sectional survey in February-March 2009, questioning 246 nurses and 270 nurse assistants in 20 nursing homes. Methods: Twelve nurses represented nursing homes in an expert meeting and listed all barriers that might cause suboptimal medication management. Based on the results, a survey was developed in which respondents could indicate whether they were involved in a particular stage of the medication process and if yes, rate the relevance of the barriers in that stage on a continuous scale, varying from 1 = no barrier to 10 = strong barrier. Barriers scored 7 or more were defined as strong. Findings: Nurses experienced a large number of barriers to safe medication management related to the nurse, organization, interdisciplinary cooperation, or to the patient and family. In preparing medication, medication administration and monitoring, being interrupted, not knowing enough on interactions, and barriers in interdisciplinary cooperation caused the most hindrance. In general, barriers in medication monitoring scored the strongest. Conclusions: In order to improve safe medication management by tailored interventions in nursing homes, through the use of a standard questionnaire, nurses and nurse assistants can give an overview of barriers they experience and rate their relevance. Nurses and nurse assistants had different opinions on the relevance of barriers, especially in the stage of medication monitoring. Job expectations in medication management were not always clear, creating additional barriers in medication safety. Clinical Relevance: This study provides an overview of potential barriers to safe medication management in nursing homes, which can be addressed in practice. The relevance scoring of the barriers enables prioritization.