Background: Encouraging patient engagement can facilitate effective medication management. Nurse plays an essential role in medication administration, teaching, and evaluating the effectiveness of medications in restoring or maintaining health. Aim: explore barriers and enhancers associated with patients and nurses participation in medications safety. Design: A descriptive exploratory study design used to achieve the aim of this study. Methods: This study was conducted at seven intensive care units affiliated to Nasser Institute Hospital. Subjects: A purposeful sample of 100 adults patients and 75 nurses working in intensive care units were included in the study. Tools: 1) Patient‟s medications safety knowledge questionnaire. 2) Self administered nurses‟ knowledge assessment questionnaire. 3) Nurse's practices observational checklist. Results: Approximately three quarters of the studied patients had unsatisfactory level of total knowledge regarding safe handling of the medications. More than two thirds of the studied patients demonstrated that there are barriers can prevent them from practicing their role in taking medication safely. Three quarters of the studied patients demonstrated that there are enhancers can help them practicing their role in the safe handling of medication. Total unsatisfactory level of nurses‟ knowledge regarding safe administration of the medications and patient‟s participation was one third. Less than two thirds of the studied nurses had barriers that prevent them from practicing their role in the safe administration of the medications. Majority of the studied nurses about more four fifth had enhancers that help them to practice their role in the safe administration of the medications. Total satisfactory level of nurses‟ practice regarding giving medications was half of studied sample. Conclusion: The result of this study concluded that there were barriers affect patient‟s participation in medication safety such as (physical/health, psychological, social, economic, and cultural, nurse/physician/clinical pharmacist, medication). There were enhancers affect patient‟s participation related to (nurses/physicians, social, medication). Barriers that affect nurse‟s participation were related to (nurses, physician, medication, work environment, and patients). Enhancers that affect nurse‟s participation related to (physicians/ pharmacist, work environment). Recommendation: This study recommends conducting periodical educational program for patients and nurses to improve their knowledge about participation in medication safety taking into consideration barriers and enhancers associated with medication safety