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Background: As an antibiotic, vancomycin presents numerous benefits in controlling methicillinresistant staphylococcal infections; however, if used inappropriately, it can lead to bacterial resistance in patients. The current study aimed to evaluate the financial burden of inappropriate use of Vancomycin in patients with cancers in selected university hospitals in Shiraz. Methods: This descriptive cross-sectional study was conducted in 2017-2018. The required data were collected using a checklist. In total, 150 adult patients with cancer were selected by the census method. moreover, the t-test, Chi-squared test, and Analysis of Variance (ANOVA) were used to examine the relationship between the study variables where appropriate. Results: The present study results suggested that inappropriate prescribing of vancomycin had a frequency of 61 (59.2%) in Namazi Hospital and 22 (46.8%) in Amir Hospital; thus, there was no significant difference between these hospitals concerning the types of prescriptions (P=0.15). It was also found that the inappropriate use of vancomycin cost the patients $1974.2 and $1046.5 in Namazi and Amir hospitals, respectively. Conclusion: The present study data indicated that the most frequent problems were the inappropriate prescription of vancomycin in hematology wards, the lack of drug discontinuation at the proper time, and the continuation of drug administration more than the patients’ needs. Thus, conducting regular educational programs for physicians per relevant guidelines could help reduce unreasonable administration of the drug and the financial burden imposed on patients.