BACKGROUND: The International Trachoma Initiative (ITI) trachoma control programme based on the SAFE strategy (Surgery, Antibiotics, Facial cleanliness and Environmental improvement) was implemented in 2002 in two rural Ethiopian zones, with mass delivery of azithromycin starting in 2003. We evaluate the impact of combined antibiotic and health educational interventions on active trachoma and Chlamydia trachomatis detected from ocular swabs, in children aged 3-9 years. Method Three-year follow-up cross-sectional survey was carried out in 40 rural Ethiopian communities to evaluate the programme. Households were randomly selected and all children were invited for eye examination for active trachoma. In 2005, eye swabs were taken for Polymerase Chain Reaction (PCR) detection of ocular C. trachomatis DNA. Adult knowledge and behaviour related to trachoma were assessed. RESULTS: Community summarized mean prevalence, overall, was 35.6% (SD = 17.6) for active trachoma, 34.0% (18.7) for trachomatous inflammation, follicular (TF) alone and 4.3% (5.3) for PCR positivity for C. trachomatis. After adjustment, odds of active trachoma were reduced in communities receiving antibiotics and one or two educational intervention components (OR = 0.35, 95% CI: 0.13-0.89 or OR = 0.31, 0.11-0.89, respectively). The odds of being PCR positive were lower in these intervention arms, compared with control (OR = 0.20, 0.06-0.62 and OR = 0.07, 0.02-0.30, respectively). Knowledge of treatment and preventative methods were reported with much higher frequency, compared with baseline. CONCLUSIONS: Trachoma remains a public health problem in Ethiopia. Antibiotic administration remains the most effective intervention but community-based health education programmes can impact, to additionally reduce prevalence of C. trachomatis.