Objective: To explore the national survey of medication safety practices with an emphasis on environmental factors and staff competencies at primary healthcare centers (PHCs) and community pharmacies (CPs) in Saudi Arabia, Riyadh city. Method: This is a 4-month cross-sectional medication safety practice survey conducted at pharmacies of PHCs of Ministry of Health and CPs in Riyadh city. The survey consisted of the modified version of the Medication Safety Self-Assessment® for Community/ Ambulatory Pharmacy from the Institute of Safe Medication Practices (ISMP). The survey consisted of a demographic section and 10 domains with questions on environmental factors, staff competency and education. The authors distributed the questionnaire and followed-up on a daily basis by physically visiting or via telephonic call. The survey was prepared in an electronic format and it was analyzed through the Survey Monkey system and Microsoft Excel version 10. Result: 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%) (95% confidence interval (95% CI) = 2.55–2.95; P<0.05; range = 2.04–3.38). The average score of all ISMP-self assessment of medication safety items at CPs was 3.14 ± 0.42 (62.86%) (95% CI = 2.90–4.38; P<0.05; range = 2.40–3.88). The average score of environmental factors, workflow and staffing domain at PHCs was 2.7 ± 0.45 (54%) (95% CI = 2.53–2.87; P<0.05; range = 1.55–3.68), whereas in CPs, the average score was 3.58 ± 0.43 (71.6%) (95% CI = 3.44–3.717; P<0.05; range = 2.63–4.37). The average score of staff competency and education at PHCs was 3.02 ± 0.298 (60.4%) (95% CI = 2.9–3.2; P<0.05; range = 2.64–3.55), whereas in the CPs, the average score was 4.15 ± 0.20 (83%) (95% CI = 4.03–4.27; P<0.05; range = 3.78–4.53). Conclusion: The PHCs implemented only half of the environmental factors, workflow and staff competency domains preventive measures for medication safety and lower than CPs. Targeting of improving environmental culture and staff competency for medication safety at PHCs is highly recommended in KSA.