A multicentre double-blind controlled clinical trial was carried out to compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg plus minocycline 100 mg (ROM) administered as single dose with that of the standard six-month WHO/MDT/PB regimen. The subjects included 1483 cases with one skin lesion who were previously untreated, were smear-negative, and had no evidence of peripheral nerve trunk involvement, and they were randomly divided into study and control groups. The total duration of the study from the day of intake was 18 months, and 1381 patients completed study. Only 12 patients were categorized as treatment failure and no difference was observed between the two regimens. Occurrence of mild side-effects and leprosy reactions were minimal (less than 1%) in both groups. This study showed that ROM is almost as effective as the standard WHO/MDT/PB in the treatment of single lesion PB leprosy.