Multiple myeloma is a plasma cell malignancy that leads to bone pain, pathological fracture, anaemia, renal failure and recurrent bacterial infections. Recently, thalidomide has demonstrated significant activity in the treatment of multiple myeloma in various western studies. In India there are very minimal studies about multiple myeloma. To study the clinical profile of multiple myeloma and the effect of thalidomide based treatment on its outcome in the Indian scenario are the aims and objective of the study. A total of 25 multiple myeloma cases were enrolled in the study. The diagnosis of multiple myeloma was made based on the presence of greater than 10% plasma cells on bone marrow, an M band in serum electrophoresis and/or a skeletal survey revealing osteolytic lesions. All the above patients were treated with tablet thalidomide 200 mg once daily on all days and tablet dexamethasone 40 mg once daily on days 1-4, 9-12, 17-20 in a 28 days cycle for 4 cycles. At the end of four cycles, all patients were re-evaluated and the response rate was assessed. The most common clinical presentation (56%) was bone related like bony swelling, bone pain, low backache and pathological fractures. The overall response rate to thal-dexa regimen was 72% (n=18). Out of these, 10 patients (56%) had complete response and 8 patients (44%) had partial response. The mean bone marrow plasma cell percentage at the end of therapy was 2% compared to 56% before therapy which was significant (p < 0.0001). None of the patients developed neutropenia or thrombocytopenia during treatment. Although multiple myeloma has remained an incurable disease to date, presently available thalidomide based combination chemotherapy represents an active inductive regimen to improve the outcome and achieve eventual cure.