Background Cefepime is essentially used for life‐threatening infections. Although overutilisation of antibiotics is strongly discouraged around the world, they are still overused in developing countries including Sudan. Objectives This study aims to evaluate the rational use of cefepime at Khartoum North Teaching Hospital‐Sudan. Methods A retrospective cross‐sectional, hospital‐based study was conducted in the internal medicine ward at Khartoum North Teaching Hospital from August/2018 to April/2019. The study covered medical records of adult patients receiving cefepime during the study period. Patient's data were analysed using simple descriptive statistics (frequency and percentage) and inferential statistics (logistic regression) to describe the relationship between dependent and independent variables. P ≤ .05 was considered statistically significant. Results Out of 90 patients, only 16.7% of patients were tested for antibiotic sensitivity. Cefepime was prescribed to 50% and 23.3% of patients for the treatment of UTIs/post‐dialysis and sepsis, respectively. Although the majority of patients (72.2%) received cefepime with appropriate indication, only 21.1% and 15.6% received the drug with appropriate dose and duration, respectively. Cefepime had been prescribed appropriately in a correct dose, duration, and indications for only 7.8% of patients. The vast majority of patients tested for kidney functions had elevated creatinine levels (96.1%); however, cefepime dose had been adjusted for only 4.1% of them. Conclusion This study highlighted the irrational use of cefepime regarding inappropriate dose, duration, and inadequate antibiotic sensitivity tests. A lack of attention to dosage adjustment in patients with renal impairment had been observed. Positive clinical outcome was significantly associated with antibiotic sensitivity test.