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Objective: Pseudomonas aeruginosa is a common cause of nosocomial infections worldwide. Increasing in the emergence and spread of multidrug-resistant (MDR) strains is a serious health concern. The aim of the present study was to determine the antibiotic resistance pattern of P. aeruginosa isolated from clinical samples. Materials and Methods: The current retrospective cross-sectional study was conducted at a tertiary-care hospital in Oman. The data of P. aeruginosa isolates identified during 2015-2019 at Sohar Hospital were retrieved from Al-Shifa computerized data system. The data were systematically analyzed using SPSS 22 software system, IBM Chicago. Descriptive statistics were applied to find frequencies and percentages. Trends were analyzed using a one-sample Chi-square test. Results: A total of 5865 P. aeruginosa strains identified in clinical samples of 4024 patients were studied. The frequency of isolation of P. aeruginosa was more among people aged >60 years (33%). The rate of isolation was significantly high (47%) in pus/wound swabs. The overall resistance of P. aeruginosa was low to moderate (10%-30%) to commonly used anti-pseudomonal drugs. Among, 10% were MDR strains. The lowest resistance (10%) was observed to piperacillin-tazobactam (TAZP), while significantly high resistance (29%-30%) was exhibited by carbapenems. Furthermore, strains isolated from respiratory secretions and urine samples have shown a significantly high percentage of resistance compared to others. Conclusions: Piperacillin-tazobactam is recommended as the drug of choice for treating especially severe Pseudomonas infections. Moderate resistance to carbapenems is an alarming sign. This pattern of resistance suggests the probable overuse of drugs. Therefore, it emphasizes strict antibiotic policy, rapid detection, and continuous monitoring of drug-resistant strains, and timely dissemination of the resistant report to clinicians. [ABSTRACT FROM AUTHOR]