OBJECTIVES:  The first Therapeutic Drug Monitoring (TDM) program started at Ministery of Health hospital in King Saud Medical City in Riyadh, Saudi Arabia. The objective of the study to assess the clinical and economic outcomes of pharmacist intervention in Therapeutic Drug Monitoring system at medical city in Riyadh city, Saudi Arabia METHODS: It is cross-sectional study of three months period with trained pharmacist in therapeutic drug monitoring and supervised by expert critical care clinical pharmacist. The pharmacist monitored all patients had Gentamicin or Vancomycin order at surgery and orthopedic wards. The pharmacist documented intervention used an International Study Model (Kinky et al., Ann Pharmacother 1999), measure level of activity, rational of clinical intervention, recommendation, patient outcome and PharmacoEconomic impact. The estimated cost valuation expressed in USD. RESULTS: In the study period the total number of pharmacist interventions were 164. Of those 124 (75.61%) interpreted with male, and 40 (24.39%) with female. The majority of them were in age (18-40 years) 92 (56.1%) followed by age (40-65) 42 (25.61%). The Most drug had interventions was Gentamicin 141 (85.98%) followed by Vancomycin 23 (14.02%). The highest interventions were potentially significant 104 (63.41%) and neutral 53 (32.32%). The most patient outcome was unknown 62 (37.8%), therapeutic end point reached 41 (25%), and patient condition improved 38 (23.17%). The most PharmacoEconomic impact was the patient length of hospital stay decreased 89 (54.27%), and reduction in the cost drug therapy monitoring 46 (28.05%). The estimated cost avoidance in the study period was (87,717.08 USD), and the total annual estimated cost avoidance (350,856.32 USD) CONCLUSIONS: Therapeutic Drug Monitoring pharmacist had the significant impact on patient condition and outcome, decrease a length of hospitalization, and avoid unnecessary an additional cost. The TDM program should apply in all clinical pharmacy services and at all hospitals in Saudi Arabia