Objective: To explore the national medication safety practice in terms of medication preparation and dispensing at Primary Healthcare Centers (PHCs) and Community Pharmacies (CPs) in Riyadh, Kingdom of Saudi Arabia. Methods: This is a 4-month cross-sectional medication safety practice survey conducted at PHCs and CPs in Riyadh. The survey consisted of the modified version of the Medication Safety Self-Assessment® for Community/Ambulatory Pharmacy from the Institute for Safe Medication Practices (ISMP). The survey consisted of a demographic section and 10 domains with 198 questions. The 10 domains included patient information; drug information; communication of drug orders and other drug information; drug labeling, packaging and nomenclature; use of medical devices; environmental factors; staff competency and education; patient education; quality processes; and risk management. This study emphasizes on the medication preparation and dispensing as per the Medication Safety Self-Assessment for Community/Ambulatory Pharmacy, Riyadh. Results: The survey was distributed to 13 PHCs and 23 CPs. The average score of all the ISMP self-assessment of medication safety items at PHCs was 2.75±0.36 (54.94 %) with 95% confidence interval (95% CI) = 2.55–2.95 (
P<0.05; range = 2.04–3.38). The average score of all the ISMP self-assessment of medication safety items at CPs was 3.14±0.42 (62.86%) with 95% CI = 2.90–4.38 (P<0.05; range = 2.40–3.88). The average score of the communication of drug orders and other drug information domain at all hospitals were 2.57±0.38 (51.4 %) with 95% CI = 2.36–2.78 (P<0.05; range = 1.92–3.25) at PHCs and in the CPs, it was 2.44±0.35 (48.8 %) with 95% CI = 2.245–2.635 (P<0.05; range = 2.00–3.09). The average score of drug labeling, packaging and nomenclature domain at all hospitals was 2.57± 0.41 (51.4 %) with 95% CI = 2.35–2.79 (P<0.05; range = 1.83–3.08) at PHCs and in CPs, it was 3.2±0.59 (64%) with 95% CI = 2.89–3.51, (P<0.05; range = 2.20–4.05). Conclusion: Fifty percent of medication safety critical elements of ISMP standards was implemented during the preparation and dispensing of medication in the PHCs and CPs. Targeting to improve medication safety key at PHCs and CPs to prevent drug-related problems is required in the Kingdom of Saudi Arabia.