Background External genital warts (EGWs, condylomata acuminata) are a common, highly contagious disease caused by human papillomavirus (HPV), predominantly HPV 6 and HPV 11. Green tea catechins have been identified for their immunostimulatory, antiproliferative and antitumour properties. Two phase III trials evaluated treatment of EGWs with ointment containing a mixture of green tea catechins (Polyphenon E), U.S. adopted name: sinecatechins). Objectives To obtain additional data on the efficacy and safety of Polyphenon E ointment in the treatment of EGWs from two randomized, double-blind, vehicle-controlled trials. Methods Men and women aged > or = 18 years (n = 1005), with two to 30 EGWs (12-600 mm(2) total area) applied vehicle (G(Veh); n = 207), Polyphenon E ointment 10% (G(10%); n = 401) or Polyphenon E ointment 15% (G(15%); n = 397) three times daily until complete clearance of all EGWs (baseline + new EGWs) or for a maximum of 16 weeks. Results A total of 1004 patients were evaluable for safety and 986 for efficacy; 838 completed treatment after 16 weeks. Complete clearance of all EGWs was obtained in 53.6% (G(10%)) and 54.9% (G(15%)) of patients with Polyphenon E vs. vehicle (35.4%) (P < 0.001). Statistically significant differences in clearance rates appeared after 6 weeks of active treatment. Odds ratios vs. G(Veh) for G(10%) [2.10; 95% confidence interval (CI) 1.49-2.98] and G(15%) (2.22; 95% CI 1.57-3.14) indicated about a twofold higher chance of complete clearance under active treatment. Time to complete clearance was shorter with active treatment (hazard ratios 1.57 and 1.87, respectively, for G(10%) and G(15%) vs. G(Veh) groups; P < 0.001). Recurrence rates during follow-up were low and similar across groups: 5.8%, 6.8% and 6.5% (G(Veh), G(10%) and G(15%) groups, respectively). Adverse events were evenly distributed across groups ( approximately 30% of patients). Severe local signs were more frequent but moderate in the active treatment groups (1.5%, 9.2% and 13.5% for G(Veh), G(10%) and G(15%) groups, respectively). Conclusions Polyphenon E ointment is effective and well tolerated in the treatment of EGWs.