Background: Indiscriminate use of corticosteroids, widespread use of broad-spectrum antibiotics, increase in the pool of immunocompromised patients and development of drug resistance has made treatment of superficial fungal infections challenging with increased rates of recurrence. There is an utmost need for novel drug combinations and improved treatment strategies to tackle this complex situation. Objective: To compare the efficacy of oral isotretinoin (20mg/day) and itraconazole (200mg/day)combination with salicylic acid 30% chemical peel for Tinea corporis and Tinea cruris. Methods: A non-randomized comparative trial was done. Adult patients between the age of 20-40 years. The diagnosis of Tinea corporis and Tinea cruris was confirmed by performing a KOH preparation. Patients with history of liver or kidney disease, diabetes, hypertension, those on corticosteroids or immunosuppressive therapy, pregnant and lactating women were excluded from the study. Outcome measure was change from baseline inerythema, scaling, pruritus and vesicles at one month. Skin scrapings for potassium hydroxide preparation (KOH) were obtained at baseline and at end of intervention (1 month). Clinical cure was defined as an absence of classical signs and a negative KOH preparation at one month. Difference in means between the two groups were compared with paired t-tests. Chi-square tests were used for proportions. Comparisons of the mean change in continuous measures between trial groups and associated 95% confidence intervals were based on linear regression with a robust variance estimator. Results: Within each group, there was a significant improvement (P<0.001) in erythema, scaling, pruritus and vesicles within after one month of intervention. Between the groups, there was a significantly greater improvement in erythema in Group 2 by a factor of 0.457(95% CI, 0.088-0.825, P=0.017). Improvement in scaling was more in Group 2 by a factor of 0.17, but the difference between the groups was not statistically significant (Paired t-test, P=0.381). The improvement in vesicles was not statistically significant between the two groups (Paired t-test, P=0.571). At study endpoint, 32(91%) patients in Group 1 and 26(74%) patients in Group 2 had a negative KOH preparation. Liver functions were not deranged in any patient on itraconazole therapy at 2weeks. Conclusion: Oral combination of itraconazole and isotretinoin was more effective in achieving microbiological eradication than salicylic acid 30% chemical peel for Tinea corporis and cruris.