INTRODUCTION: Trachoma is caused by the bacterium Chlamydia trachomatis (Ct). The WHO recommends the SAFE strategy for trachoma elimination: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Multiple rounds of SAFE implementation have proven insufficient to eliminate trachoma in Ethiopia, where over 50% of the global trachoma burden remains. More effective antibiotic treatment schedules and transmission-suppressing approaches are needed. The aim of stronger SAFE is to evaluate the impact of a novel package of interventions to strengthen the A, F and E of SAFE on the prevalence of ocular Ct and trachoma in Oromia, Ethiopia. METHODS AND ANALYSIS: 68 clusters were randomised in a 1:1:1:1 ratio to one of (1) standard A/standard F&E (standard SAFE), (2) standard A/enhanced F&E, (3) enhanced A/standard F&E or (4) enhanced A/enhanced F&E (stronger SAFE). Enhanced A includes two height-based doses of oral azithromycin (equivalent to 20 mg/kg) given as single doses 2 weeks apart, as mass drug administration, annually. Enhanced F&E includes fly control measures (permethrin-treated headwear and odour-baited traps) and face-washing hygiene behaviour change implemented at household level in selected communities. The interventions will be implemented and reinforced over 3 years.The primary outcome is the prevalence of ocular Ct by quantitative PCR in children aged 1-9 years at 36 months. A key secondary outcome is the prevalence of active (inflammatory) trachoma in the same children, assessed by validated trachoma graders and conjunctival photography. Laboratory technicians and photo-graders are masked to treatment allocation. Other important secondary analyses include process evaluations, assessment of behaviour change, fly indicators, adherence and coverage of interventions and a cost analysis. ETHICS AND DISSEMINATION: Study protocols have been approved by the National Research Ethics Review Committee of the Ethiopian Ministry of Science and Higher Education and the London School of Hygiene & Tropical Medicine Ethics Committee. An independent data safety and monitoring board oversees the trial. Results will be disseminated through peer-reviewed publications, presentations and reports. TRIAL REGISTRATION NUMBER: ISRCTN40760473.