BACKGROUND: Children initially hospitalized with severe anaemia in Africa are at high risk of readmission or death within 6 months after discharge. No intervention strategy specifically protects children during the post-discharge period. Recent evidence from Malawi shows that 3 months of post-discharge malaria chemoprevention (PMC) with monthly treatment with artemether-lumefantrine in children with severe malarial anaemia prevented 31% of deaths and readmissions. While a confirmatory multi-centre trial for PMC with dihydroartemisinin-piperaquine is on going in Kenya and Uganda, there is a need to design and evaluate an effective delivery strategy for this promising intervention. METHODS: This is a cluster-randomized trial with 5 arms, each representing a unique PMC delivery strategy. Convalescent children aged less than 5 years and weighing more than 5 kg admitted with severe anaemia and clinically stable are included. All eligible children will receive dihydroartemisinin-piperaquine at 2, 6 and 10 weeks after discharge either: 1) in the community without an SMS reminder; 2) in the community with an SMS reminder; 3) in the community with a community health worker reminder; 4) at the hospital with an SMS reminder; or 5) at the hospital without an SMS reminder. For community-based strategies (1, 2 and 3), mothers will be given all the PMC doses at the time of discharge while for hospital-based strategies (4 and 5) mothers will be required to visit the hospital each month. Each arm will consist of 25 clusters with an average of 3 children per cluster giving approximately 75 children and will be followed up for 15 weeks. The primary outcome measure is uptake of complete courses of PMC drugs. DISCUSSION: The proposed study will help to identify the most effective, cost-effective, acceptable and feasible strategy for delivering malaria chemoprevention for post-discharge management of severe anaemia in under-five children in the Malawian context. This information is important for policy decision in the quest for new strategies for malaria control in children in similar contexts. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02721420 . Protocol registered on 29 March 2016.The study was not retrospectively registered but there was a delay between date of submission and the date it first became available on the registry.