As progress to eliminate trachoma is made, addressing hard-to-reach communities becomes of greater significance. Areas in Tanzania, inhabited by the Maasai, remain endemic for trachoma. This study assessed the effectiveness of Mass Drug Administration (MDA) through an ethnographic study of trachoma amongst a Maasai community. The MDA experience in the context of the livelihoods of the Maasai in a changing political economy was explored using participant observation and household interviews. Factors influencing MDA effectiveness within five domains were analysed. 1) Terrain of intervention: Human movement hindered MDA, including seasonal migration, domestic chores, grazing and school. Encounters with wildlife were significant. 2) Socio-cultural factors and community agency: Norms around pregnancy led women to accept the drug but hide refusal to swallow the drug. Timing of Community Drug Distributor (CDD) visits conflicted with livestock grazing. Refusals occurred among the ilmurrani age group and older women. Mistrust significantly hindered uptake of drugs. 3) Strategies and motivation of drug distributors: Maa-speaking CDDs were critical to effective drug delivery. Maasai CDDs, whilst motivated, faced challenges of distances, encounters with wildlife and compensation. 4) Socio-materiality of technology: Decreases in side-effects over years have improved trust in the drug. Restrictions to swallowing drugs and/or water were relevant to post-partum women and the ilmurrani. 5) History and health governance: Whilst perceptions of the programme were positive, communities questioned government priorities for resources for hospitals, medicines, clean water and roads. They complained of a lack of information and involvement of community members in health care services. With elimination in sight, hard-to-reach communities are paramount as these are probably the last foci of infection. Effective delivery of MDA programmes in such communities requires a critical understanding of community experiences and responses that can inform tailored approaches to trachoma control. Application of a critical social science perspective should be embedded in planning and evaluation of all NTD programmes.