In the 1970s, the WHO embarked on an ambitious project to promote primary health care worldwide. The Expanded Programme on Immunization (EPI) was one of the most successful parts of that effort, yet some national EPIs struggled to increase vaccination coverage while others were very successful. Drawing on documentary sources from the WHO Archives and Library, this paper traces the historical development of global EPI policy and compares the development of two programs: the high-performing EPI in Malawi and the low-performing one in Cameroon. Global advisers’ rigid adherence to then-current global policy and blindness to local conditions and historical legacies exacerbated problems faced by Cameroon's EPI, helping explain that program's weakness. In Malawi, in contrast, the similarity of global policy and local practices helped strengthen the EPI. Greater flexibility in pursuing program goals and attention to historical legacies could help future programs avoid similar counterproductive dynamics.