OBJECTIVES: To explore the adherence of Vancomycin therapeutic monitoring guidelines in Saudi Arabia METHODS: a prospective study of vancomycin guidelines adherence. It conducted over a 3-Month at King Saud Medical City (KSMC). The guidelines based on Central Diseases Control and American Society of Health-System Pharmacist. Any patient received vancomycin followed up by trained pharmacist. He followed the following elements including; FDA labeled indication, all details such as weight, height, bug culture sensitivity, any adjustments in dosage, trough levels and duration of administration recorded on a TDM form on a systematic basis. All data gathered were statistically evaluated using SPSS version 22. RESULTS: Results the total number of patients 53, which 34 (64.15%) were male and 19 (35.85%) were female with a mean age of 36.21 ± 16.4 years. Of those; 18 (33.96%) patients from General Surgery wards and 35 (66.04%) patients from orthopedic wards. Twenty-nine (54.7%) non-adherence to indications guidelines while 24 (45.3%) adherence to an indication. All patients 53 (100%) were non-compliance of vancomycin duration of administration time. The levels of vancomycin were sub-therapeutic level in 23 (43.4%) patients, 9 (17%) patients above therapeutic levels, and 10 (18.9%) patients have not checked the drug levels. The sampling time 22 (41.5%) Patients were wrong, 16 (30.18%) patients were correct, and 10 (18.9%) patients not documented. CONCLUSIONS: There was indigent adherence to international guidelines of Vancomycin. Targeting compliance, the guidance leads to decrease multi-drug resistance, improve patient therapeutic outcome, prevent the drug-related problem and avoid the unnecessary additional cost.