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Background: Most hospitalized patients experience Drug Therapy-Related Problems (DTRPs) resulting in morbidity, mortality, and an increase in the cost of treatment. DTRPs are an important issue and a serious yet preventable problem. Objective: To identify DTRPs in the department of critical care medicine of a tertiary care center in Nepal. Methods: This was a cross-sectional study carried out at the department of critical care medicine in a tertiary care hospital in Kathmandu, Nepal from August to November 2021. All the patients admitted to ICU/ high care unit (HCU) for more than 48 hours during the study period were recruited in this study. Two clinical pharmacists visited the ICU/ HCU daily to identify any drug therapy-related problems. The Pharmaceutical Care Network Europe (PCNE) Classification system version 9.1 was referred for the classification of identified DTRPs. Descriptive statistics were applied for demographic variables. The Chi-square test was used for categorical variables. Pearson correlation was used to study the relationship between patient variables and the number and types of DTRPs. Results: DTRPs were identified in 74.2% (n=89) of patients. More than one DTRP was identified in 38.5% of patients. The identified DTRPs were primarily classified into two sections: Problems and Causes. A total of 106 problems were identified among which unnecessary drug treatment (40.5%, n=43) was the most common problem. For the causes: total of 137 were identified, out of which the drug and dose selection accounted for 44.5 and 16.8%, respectively. The average DTRP per patient was 1.5± 0.7. Antibiotics 30 (22%) and multivitamins, 10 (7%) were the maximal involved in DTRPs. More DTRPs were observed in male patients (n=60, 80%). The association between dose selection and gender was significant. Drug selection issues were observed more in patients prescribed multiple drugs and with a shorter hospital stay. Conclusion: Most DTRPs identified in the study were those that could be prevented. More focus is needed on antibiotic usage in the ICU and special monitoring measures are needed for vulnerable patient groups such as the elderly. Inclusion of more clinical pharmacists can help to identify and mitigate DTRPs. [ABSTRACT FROM AUTHOR]