AIMS: The WHO recommends the SAFE (surgery, antibiotics, facial cleanliness and environmental improvement) strategy for trachoma control. We aimed to investigate the association between active trachoma and community intervention with antibiotics, facial cleanliness, environmental improvement (A,F,E) components of SAFE in five trachoma hyperendemic districts of Amhara region, Ethiopia. METHODS: Cluster random surveys were undertaken to evaluate SAFE following 3 years of interventions. Children aged 1-9 years were examined for trachoma signs using the WHO simplified grading system and structured questionnaires used to assess uptake of A, F and E. Active trachoma signs (trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI)) were used to derive an ordinal severity score where TI was considered more severe than TF. Associations between active trachoma and potential factors were investigated using ordinal logistic multilevel regression models. RESULTS: A total of 1813 children aged 1-9 years were included in the analysis. Factors independently associated with reduced odds of active trachoma signs were: number of times treated with azithromycin (p-trend=0.026); months since last mass azithromycin distribution (p-trend<0.001); clean face (OR=0.6; 95% CI 0.5 to 0.8); and household pit latrine (OR=0.8; 95% CI 0.7 to 0.9). CONCLUSION: These findings are important, since they make the case for continued implementing the A,F,E interventions simultaneously, and suggest appropriate timing of SAFE evaluations within 6-12 months after the last mass azithromycin distribution.