OBJECTIVE To determine the safety, efficacy, and acceptability of self-administered podofilox for treatment of genital warts when used in everyday circumstances.DESIGN Prospective cohort study.SETTING National convenience sample of 1361 patients enrolled through 453 physicians who frequently treat genital warts.PATIENTS Serial enrollment of patients being treated for the first time or who had completed another treatment with unsatisfactory results. After initial examination, patients used podofilox for up to four cycles (each consisting of 3 days of treatment, 4 days without). At the end of each week, patients completed a diary detailing response and symptoms. After 4 weeks, patients returned to the physician for reevaluation. Brief follow-up questionnaires were also obtained 8 and 12 weeks after initiating therapy.RESULTS At 4 weeks, the end of the main evaluation period, 53% of patients reported complete clearing, and another 28% clearing of at least half their warts. The most common side-effects were pain and burning, and redness and swelling. Side-effects were most frequent and most severe during the first week of use. Overall assessment by physicians and patients was favorable, with 65% and 70%, respectively, considering podofilox to be better than other treatments. Patient comments indicated that an advantage of podofilox treatment was that repeated physician visits were unnecessary.CONCLUSIONS In typical conditions of use among large numbers of subjects, podofilox is effective and well tolerated. The strongest virtue of self-treatment with podofilox may be that it offers a less costly and more flexible method of treatment, a benefit of particular interest for managed care settings.