Background: Although drug-induced liver injury (DILI) is a rare clinical event, it carries significant morbidity and mortality. The diagnostic approach of DILI is still challenging because of lack of reliable markers that would allow distinguishing DILI from other causes of liver injury. Objective: To study the demographic, clinical and laboratory characteristics, and their relation to outcome of patients with DILI. Patients and Methods: Case control study conducted on 80 participants divided into two groups; Group I 40 patients with acute DILI and Group II 40 patients with acute viral induced liver injury. Subjects were systematically evaluated for clinical and laboratory characteristics, other etiologies, severity of DILI with application of Roussel Uclaf Causality Assessment Method (RUCAM) and liver biopsy whenever feasible and were all followed for 6 months thereafter. Results: Diclofenac was the most incriminated drug in DILI group (16 cases, 40%). Hepatocellular injury pattern was more common (28 cases, 70%). Infection with acute hepatitis B virus (HBV) and hepatitis A virus (HAV) were the commonest etiology of viral hepatitis (32 cases, 80%). All patients with acute viral hepatitis, improved with no recorded mortality nor chronicity. While 6 patients (15%) with DILI died. Conclusion:  The diagnostic approach of DILI is still rudimentary and inaccurate and require high index of suspicion and thus, careful assessment is required to distinguish DILI from other causes of liver injury.