Objectives: The primary aim of this study was to estimate cost-efficiency of clinical pharmacy services in Saudi Arabia by using American model. Methods: This is a simulation study which includes data of all 5 months of providing clinical pharmacy services for adults organized by local drug information center at biggest public hospital in Riyadh city. Ten clinical pharmacists and expert trained pharmacists provided clinical pharmacy services at the hospital including drug information services, poisoning control services, therapeutic drug monitoring services, orthopedic services, oncology services, Pharmacoeconomical services and pain management services. All pharmacists should document the clinical pharmacy activities on a monthly basis. The estimated cost avoidance was calculated by using two International Studies Models, expressed in US dollars (USDs). The cost considered were the expected results of drug-related inquiries, poisoning information calls if not resolved and pharmacist intervention for all other clinical pharmacy services. Results: The total average estimated monthly cost avoidance from all clinical services (17,554,931.46 USD) with cumulative cost avoidance was 65,830,992.97 USD during the study period. The estimated total cost avoidance annually was 210,659,177.52 USD. The highest cost avoidance came from poisoning services, whose estimated cost avoidance was 61.8% (9,110,026.40 USD) followed by drug information services, whose estimated cost avoidance was 26.8% (4,711,273.50 USD) and other clinical pharmacy services, whose estimated cost avoidance was 11.4% (2,006,444.63 USD). Each USD invested in the clinical pharmacist estimated cost avoidance was an average of 28.76 USD. Each USD invested in the clinical pharmacist provides poisoning control services estimated cost avoidance was an average of 17.77 USD and each USD invested in the clinical pharmacist provide drug information services estimated cost avoidance was an average of 7.7 USD. Conclusion: The clinical pharmacy services had a very high economic impact on the healthcare system in the local public hospital. In the future, we are targeting to expand the clinical pharmacy services to prevent drug-related cost in the Kingdom of Saudi Arabia.