At baseline in 2006, Amhara National Regional State, Ethiopia, was the most trachoma-endemic region in the country. Trachoma impact surveys (TIS) were conducted in all districts between 2010 and 2015, following 3-5 years of intervention with the WHO-recommended SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. A multistage cluster random sampling design was used to estimate the district-level prevalence of trachoma. In total, 1,887 clusters in 152 districts were surveyed, from which 208,265 individuals from 66,089 households were examined for clinical signs of trachoma. The regional prevalence of trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense among children aged 1-9 years was 25.9% (95% CI: 24.9-26.9) and 5.5% (95% CI: 5.2-6.0), respectively. The prevalence of trachomatous scarring and trachomatous trichiasis among adults aged ≥ 15 years was 12.9% (95% CI: 12.2-13.6) and 3.9% (95% CI: 3.7-4.1), respectively. Among children aged 1-9 years, 76.5% (95% CI: 75.3-77.7) presented with a clean face; 66.2% (95% CI: 64.1-68.2) of households had access to water within 30 minutes round-trip, 48.1% (95% CI: 45.5-50.6) used an improved water source, and 46.2% (95% CI: 44.8-47.5) had evidence of a used latrine. Nine districts had a prevalence of TF below the elimination threshold of 5%. In hyperendemic areas, 3-5 years of implementation of SAFE is insufficient to achieve trachoma elimination as a public health problem; additional years of SAFE and several rounds of TIS will be required before trachoma is eliminated.