Leprosy is a chronic granulomatous disease affecting mainly the skin and cutaneous nerves, with systemic involvement to alleviate this problem, single dose ROM regimen was introduced in 1997. ROM regimen is found to be equally effective as MDT. In ROM, Ofloxacin is a racemic mixture, which consists of both dextro and levo isomers. Based on stereoisomeric theory, the levo isomer of ofloxacin (levofloxacin) is found to be more effective than racemic ofloxacin hence it was decided to find out whether levofloxacin would be more effective than Ofloxacin in Paucibacillary leprosy, through a prospective, randomized, single blind and clinical study. 72 patients were admitted into the study. 36 each were randomly allocated to the control group (ROM regimen) and the study group (RLM regimen). Clinical scoring was done before and after treatment with both the regimens. The patents were followed up every week till the end of 6 months. Results were analyzed by using Fisher's exact test. From this study, it was found that levofloxacin in RLM regimen has resulted in complete cure in 75% of patients whereas ofloxacin in ROM regimen cured only 36.1% of patients. Hence it can be concluded that levofloxacin (L-ofloxacin) is more effective than ofloxacin in leprosy. It is free from any side effects and it can be substituted for ofloxacin in the current ROM regimen for better cure. © IDOSI Publications, 2010. © 2010 Elsevier B.V., All rights reserved.