Acne is a common disease of the teenage population causing cosmetic disfigurements as well as many psychological problems in the affected persons. The main pathogenesis of the disease is the involvements of the oil glands at the base of hair follicles. The clinical lesions are usually papules and pustules over face, forehead, chest and back. In many cases conventional treatment fails and the patients become helpless in this condition. Thus in this study a possible curative role of homeopathic medicines was explored in such cases based on a pilot study done earlier at our Institute. A group of 400 such cases were enrolled in the study after consideration of all ethical issues and following inclusion and exclusion criteria formulated at our Institute. There were also a control group of 30 cases where only placebo was given which were similar in appearance containing only vehicle of the medicine. Only a single oral homeopathic medicine out of two medicines “sulphur” or “tuberculinum” was given in the test group based on clinical case history as observed in the pilot study. No local application was used in the study. Out of 400 cases 387 (96.75%) cases showed significant improvements within 6 months of treatment including cure in many cases within 3 months. The control group showed no changes even after 6 months. The results indicate a promising role of homeopathic medicines in such difficult cases.