Objectives: We sought to estimate the prevalence of HIV drug resistance and describe the common HIV genetic mutations in patients failing antiretroviral therapy (ART). We also investigated the impact of HIV resistance tests results on patients' management. Methods: We conducted a retrospective record review for all HIV genotypic resistance tests requested at the HIV clinic of a tertiary HIV center in Muscat, Oman, from April 2011 to May 2017. Results: A total of 98 genotypic resistance tests for 84 patients failing ART were analyzed; 82 tests for 69 patients (83.7%, 95% confidence interval: 76.4–91.0) showed resistance to at least one ART drug. M184V/I, K103N/S, and G190A/S/E were the most common mutations detected. Among the tests with a resistant virus, 78.0% were followed by switching ART based on the resistance test profile resulting in virus load suppression after six months in 60.9% of the cases. Conclusions: HIV drug resistance is very common among HIV patients failing ART in Oman, and should be considered in those patients. Switching ART treatment based on the resistance test result leads to a good virological response in adherent patients.