Information, behaviours, and technologies spread when people interact. Understanding these interactions is critical for achieving the greatest diffusion of public interventions. Yet, little is known about the performance of starting points (seed nodes) for diffusion. We track routine mass drug administration—the large-scale distribution of deworming drugs—in Uganda. We collect friendship networks, socioeconomic factors, and treatment delivery outcomes for 16,357 individuals in 3,491 households of 17 rural villages. Each village has two community medicine distributors (CMDs), who are the seed nodes and responsible for administering treatments. Here we show that CMDs with tightly-knit (clustered) friendship connections achieve the greatest reach and speed of treatment coverage. Importantly, we demonstrate that clustering predicts diffusion through social networks when spreading relies on contact with seed nodes whilst centrality is unrelated to diffusion. Clustering should be considered when selecting seed nodes for large-scale treatment campaigns.