Background: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities. Methods: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates. Findings: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported. Interpretation: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established. Funding: Novartis Foundation.