Background: Genital warts are a well-recognized clinical entity and a disease of great antiquity that differ from skin warts both histologically and antigenically. It is a common sexually transmitted disease of high prevalence all over the world. Women are more likely to be unaware of such warts because it is harder for them to examine their genitalia. Objective: The purpose of this multicenter, double-blind, placebo-controlled study was to compare the clinical efficacy and tolerance of 0.3% and 0.5% podophyllotoxin in a cream emulsion (castor oil, BP as vehicle) to cure genital condylomata in women. Methods: Preselected (n = 80) Asian females (mean age 23.6 years), harboring 544 warts (mean 6.8 in number), ranging from 1 to 9 mm in size (mean 2.1 mm) with biopsy-proven diagnosis of condylomata acuminata were randomly allocated to three groups (30 + 30 + 20). At home the patients applied the given trial medication themselves (using the finger) twice a day, for 3 consecutive days per week, and if not cured the same course was extended to 3 more weeks, in total 24 topical applications for 4 weeks. The patients were examined on a weekly basis, and a total regression of warts (biopsy-proven) was evaluated as complete cure. Results: By the end of the study, the placebo group (20 patients, bearing 124 warts) did not show any regression or clinical efficacy, while 41/60 patients (68.3%) and 349/420 warts (83%) were cured in the 0.3% and 0.5% treatment groups (placebo vs. active groups p < 0.001). Patients using the 0.5% active medication had substantially more eliminated warts (205/349, 95.8%) than the 0.3% group (70%). Localized adverse symptoms were mild to moderate and were well tolerated by the patients with no dropout. Forty-three patients (53.8%) did not show any adverse reaction. The most frequent adverse symptoms were tenderness (23/80, 28.8%) and burning sensation (14/80, 17.5%). Among 41/80 (51.25%) cured patients 4 had a relapse after 16 weeks. Conclusion: Along with mild, tolerable side effects the study demonstrates that 0.5% podophyllotoxin cream is more efficacious than 0.3% (p < 0.01) and can be considered as a reliable home-based treatment.