Background: There are many whitening agents for melasma treatment, but in aspects of potency and safety, few treatment agents exist. To evaluate whitening agents we previoulsy suggested a new parameter: a ratio of lesion/non-lesional melanin index (MI ratio) to compensate the seasonal effects. Objectives: In this study, we evaluated the efficacy of 4n-butyl resorcinol and resveratrol containing cream using MI ratio and compared the efficacy with other whitening agents. Methods: 21 females with melasma were enrolled. Subjects used 4n-butyl resorcinol and resveratrol containing cream for 4 weeks. Skin color of the lesional and preauricular non-lesional skin was measured with a Mexameter at baseline, week 2 and week 4, and MI ratio was obtained. To compare the efficacy with other whitening agents for melasma, MI ratio was obtained from the data of seven other clinical trials performed in Seoul National University Bundang Hospital. Results: Mean MI of lesional skin decreased from 201.1 to 189.4 at week 2 and 182.8 at week 4, and the difference was statistically significant from week 2. MI ratio decreased from 155.9% at baseline to 142.5% at week 4 (-13.4%). This result was compared with that of seven other clinical trials on whitening agents. Among eight different whitening agents, 4n-butyl resorcinol and resveratrol containing cream showed the biggest decrease of MI ratio at week 4. Conclusion: 4n-butyl resorcinol and resveratrol containing cream has fast and potent whitening effect on melasma.