This trial investigated the clinical efficacy of topical sinecatechins, a defined Camellia sinensis (green tea) extract, in the treatment of external genital and perianal warts. A double-blind, vehicle-controlled RCT was conducted involving 502 male and female patients aged 18 years and older, with 2–30 anogenital warts ranging from 12 to 600 mm² total wart area. Patients applied sinecatechins ointment 15% or 10% or vehicle (placebo) three times daily for a maximum of 16 weeks or until complete clearance of all warts, followed by a 12-week treatment-free follow-up to assess recurrence. Complete clearance of all baseline and newly occurring warts was obtained in 57.2% and 56.3% of patients treated with sinecatechins ointment 15% and 10%, respectively, compared with 33.7% for vehicle. Significance was observed at weeks 4 and 6 and all subsequent visits. Numbers needed to treat were 4.3 and 4.4. Partial clearance rates of at least 50% were reported for 78.4% and 74.0% of patients in the sinecatechins ointment 15% and 10% groups, respectively, compared with 51.5% of vehicle patients. During follow-up, recurrence of any wart was observed in 6.5%, 8.3% and 8.8% in the sinecatechins ointment 15% group, sinecatechins ointment 10% group, and vehicle patients, respectively. A total of 3.7%, 8.3% and 0.0% developed new warts, respectively. A total of 87.7% and 87.3% of patients in the sinecatechins ointment 15% and 10% groups, and 72.1% of vehicle patients experienced application site reactions; 49.2%, 46.2% and 65.4% of those, respectively, were mild or moderate.