Background: A trachoma control programme was started in southern Sudan in 2001. We did a 3-year evaluation to quantify uptake of SAFE (surgery, antibiotics, facial cleanliness, and environmental change) interventions, and to assess the prevalence of active trachoma and unclean faces. Methods: Cross-sectional surveys, including clinical assessment of trachoma (WHO simplified system) and structured questionnaires, were done in four intervention areas at baseline and follow-up. Process indicators were uptake of SAFE components; primary outcome indicators included trachomatous inflammation-follicular (TF) and unclean face in children aged 1-9 years. Findings: There was heterogeneous uptake of SAFE between intervention areas. Surgical coverage was low in all areas (range 0.5%of 428 individuals in Katigiri to 6%of 5002 in Kiech Kuon), antibiotic uptake ranged from 14%of 1257 individuals in Kiech Kuon to 75%of 954 in Katigiri, health education ranged from 49%of 190 households in Kiech Kuon to 90%of 182 in Padak, and latrine coverage from 3%of households in Tali to 16%in Katigiri. Substantial decreases in prevalence of TF and unclean faces were recorded in Katigiri and Tali, two of three sites where uptake of antibiotics and health education was high: TF decreased by 92%(95%CI 87-96) and 91%(86-95), respectively, and unclean face decreased by 87%(78-94) and 38%(22-52), respectively. Moderate effects were recorded in Padak, an area with high coverage, with a 28%(14-41) decrease in TF and a 16%(7-25) decrease in unclean face. No evidence of decline was seen in Kiech Kuon, where uptake of antibiotics and health education was low, with a 2%(-10 to 12) decrease in TF and a 10%(-3 to 23) decrease in unclean face. Interpretation: Our results show that substantial falls in active trachoma can occur where SAFE is implemented, and that good results could be achieved with the SAFE strategy in other trachomaendemic areas. Background: A trachoma control program was started in southern Sudan in 2001. We did a 3-year evaluation to quantify uptake of SAFE (surgery, antibiotics, facial cleanliness, and environmental change) interventions, and to assess the prevalence of active trachoma and unclean faces. Methods: Cross-sectional surveys, including clinical assessment of trachoma (WHO simplified system) and structured questionnaires, were done in four intervention areas at baseline and follow-up. Process indicators were uptake of SAFE components; primary outcome indicators included trachomatous inflammation -follicular (TF) and unclean face in children aged 1-9 years. Findings: There was heterogeneous uptake of SAFE between intervention areas. Surgical coverage was low in all areas (range 0.5% of 428 individuals in Katigiri to 6% of 5002 in Kiech Kuon), antibiotic uptake ranged from 14% of 1257 individuals in Kiech Kuon to 75% of 954 in Katigiri, health education ranged from 49% of 190 households in Kiech Kuon to 90% of 182 in Padak, and latrine coverage from 3% of households in Tali to 16% in Katigiri. Substantial decreases in prevalence of TF and unclean faces were recorded in Katigiri and Tali, two of three sites where uptake of antibiotics and health education was decreased: 92% (95% CI 87-96) and 91% (86-95), respectively, and unclean face decreased by 87% (78-94) and 38% (22-52), respectively. Moderate effects were recorded in Padak, an area with high coverage, with a 28% (14-41) decrease in TF and a 16% (7-25) decrease in unclean face. No evidence of decline was seen in Kiech Kuon, where uptake of antibiotics and health education was low, with a 2% (- 10 to 12) decrease in TF and a 10% (- 3 to 23) decrease in unclean face. Interpretation: Our results show that substantial falls in active trachoma can occur where SAFE is implemented, and that good results could be achieved with the SAFE strategy in other trachomaendemic areas.