Women with persistent HPV infections have increased risk of progressive CIN lesions. Transmission of HPV between sexual partners might maintain viral infection and, consequently, may influence the clinical course of CIN. We investigated the effect of condom use on regression of CIN lesions and on clearance of HPV. Women with CIN and their male sexual partners were randomized for condom use (condom group n = 72 and noncondom group n = 76). They were conservatively managed and followed every 3-6 months by colposcopy, cytology and HPV testing by GP5+/6+ PCR. Baseline cervical biopsy specimens were taken. Median follow-up time for women was 15.2 months (range 3.0-85.4). Outcomes of interest were clinical regression of CIN at colposcopy and clearance of HPV. Outcomes were assessed in 64 women of the condom group and 61 women of the noncondom group. Women in the condom group showed a 2-year cumulative regression rate of 53% vs. 35% in the noncondom group (p = 0.03). The 2-year cumulative rates of HPV clearance were 23% vs. 4%, respectively (p = 0.02). Although lower regression rates were found if women were HPV-positive and had > or =CIN2 lesions at baseline, effects of condom use were found both in women with CIN1 and in women with > or =CIN2 lesions. Condom use promotes regression of CIN lesions and clearance of HPV.