Multi-sectoral programs that involve stakeholders in agriculture, nutrition and health care are essential for responding to nutrition problems such as vitamin A deficiency among pregnant and lactating women and their infants in many poor areas of lower income countries. Yet planning such multi-sectoral programs and designing appropriate evaluations, to respond to different disciplinary cultures of evidence, remain a challenge. We describe the context, program development process, and evaluation design of the Mama SASHA project (Sweetpotato Action for Security and Health in Africa) which promoted production and consumption of a bio-fortified, orange-fleshed sweetpotato (OFSP). In planning the program we drew upon information from needs assessments, stakeholder consultations, and a first round of the implementation evaluation of a pilot project. The multi-disciplinary team worked with partner organizations to develop a program theory of change and an impact pathway which identified aspects of the program that would be monitored and established evaluation methods. Responding to the growing demand for greater rigour in impact evaluations, we carried out quasi-experimental allocation by health facility catchment area, repeat village surveys for assessment of change in intervention and control areas, and longitudinal tracking of individual mother-child pairs. Mid-course corrections in program implementation were informed by program monitoring, regular feedback from implementers and partners' meetings. To assess economic efficiency and provide evidence for scaling we collected data on resources used and project expenses. Managing the multi-sectoral program and the mixed methods evaluation involved bargaining and trade-offs that were deemed essential to respond to the array of stakeholders, program funders and disciplines involved.