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ObjectiveTo assess implementation and to identify barriers and facilitators to implementation, sustainability and scalability of an implementation strategy to provide lay health workers (LHWs) with the knowledge, skills and tools needed to implement an intervention to support patient tuberculosis (TB) treatment adherence.DesignMixed-methods design including a cluster randomised controlled trial and process evaluation informed by the RE-AIM framework.SettingForty-five health centres (HCs) in four districts in the south east zone of Malawi, who had an opportunity to receive cascade training.ParticipantsForty-five peer-trainers (PTs), 23 patients and 20 LHWs.InterventionImplementation strategy employing peer-led educational outreach, a clinical support tool and peer support network to implement a TB treatment adherence intervention.Outcome measuresProcess data were collected from study initiation to the end-of-study PT meeting, and included: LHW and patient interviews, quarterly PT meeting notes, training logs and study team observations and meeting notes. Data sources were first analysed in isolation, followed by method, data source and analyst triangulation. Analyses were conducted independently by two study team members, and themes revised through discussion and involvement of additional study team members as needed.ResultsForty-one HCs (91%) trained at least one LHW. Of 256 LHWs eligible to participate at study start 152 (59%) completed training, with the proportion trained per HC ranging from 0% to 100% at the end of initial cascade training. Lack of training incentives was the primary barrier to implementation, with intrinsic motivation to improve knowledge and skills, and to improve patient care and outcomes the primary facilitators of participation.ConclusionWe identified important challenges to and potential facilitators of implementation, scalability and sustainability, of the TB treatment adherence intervention. Findings provide guidance to scale-up, and use of the implementation strategies employed, to address LHW training and supervision in other areas.Trial registration numberNCT02533089.