Objectives: Medication safety program started at Riyadh city of Ministry of Health in 2014. Identifying, resolving and preventing drug therapy problems are the unique contributions of the pharmaceutical care practitioner. The research aimed to estimate cost-efficiency of Medication Safety program at the hospital in East province, Saudi Arabia by using American model of pharmacist intervention cost avoidance. Methods: This cross-sectional study with a 9-month recruitment period was conducted in a 300-bed public hospital through preventing and documentation of medication errors in adults and pediatrics at Ministry of Health hospitals in 2015. The program led by trained pharmacist and delivered basic patient safety in medical education to all healthcare professionals. The predictable cost calculated using International Study Model, expressed in USD, the cost measured were the expected results of medication errors outcome if not stopped; starting from physician visit, additional laboratory test, further treatment, hospital admission and critical care admission to death stage. Results: The total number of prevented medication errors were 3,378 at 805 prescribed to 805 patients with an estimated cost avoidance of avoiding medication errors was (98,195.97 USD) for the study period and (10,910 USD) per month. The pharmacist avoided medication errors with estimated cost avoidance of drugrelated problem (29 USD) per each mistake and (122 USD) per prescription and patient. The most type inquiries estimated cost avoidance was prescribing stage 86,939.05 USD (99.86%), followed by drugrelated errors 7,061.26 USD (7.2%) and dosage form-related errors 6,084.98 USD (6.2%). The highest drug of cost avoidance were Musculoskeletal and joint disease (8,397.2 USD) followed by Infections (5,731.17 USD) and Nutrition (4,717.99 USD), while the largest drug of cost avoidance was Paracetamol Injection (5,812.17 USD), followed by oral Ferrous Sulfate (3,562.79 USD) and Ceftriaxone 1g (2,861.70 USD). Conclusion: Medication safety program is a cost-efficiency simulation at the public hospital in Saudi Arabia, prevents medication disasters, improve patient safety. Increasing drug safety program associated with preventing drug-related problems and cost avoidance simulation for Healthcare development and better care and better patient consequences.