Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug-induced reaction characterized by a triad of fever, skin rash, and symptomatic or asymptomatic internal organ involvement. Aims: The aim of this study is to determine the study of varied clinical manifestations and their therapeutic outcome in patients with DRESS. Materials and Methods: A hospital-based retrospective case series was conducted in the department of dermatology. The medical records of patients with DRESS syndrome, drug reaction with eosinophilia, and drug hypersensitivity syndrome within 3 years were reviewed and were entered into a specially prepared pro forma. Results: A total of 16 patients fulfilled the criteria and were studied with equal involvement in males and females. The latency period of 4–6 weeks was the most common duration for drug exposure. Anticonvulsants were associated with more than 50% of the cases. Other than skin, hematological and hepatic involvement was noted. The topical steroids with moisturizers reduced scaling and erythema in 62.5% of the patients. Conclusion: The manifestations in DRESS can be diverse ranging from cutaneous lesions such as maculopapular rash to systemic involvement. Anticonvulsants are the most commonly implicated drug. Topical steroids are effective in patients with limited skin involvement.