BackgroundThe use of highly hazardous pesticides by smallholder farmers constitutes a classic trans-sectoral ‘wicked problem’. We share our program of research in potato and vegetable farming communities in the Andean highlands, working with partners from multiple sectors to confront this problem over several projects.MethodsWe engaged in iterative cycles of mixed methods research around particular questions, actions relevant to stakeholders, new proposal formulation and implementation followed by evaluation of impacts. Capacity building occurred among farmers, technical personnel, and students from multiple disciplines. Involvement of research users occurred throughout: women and men farmers, non-governmental development organizations, Ministries of Health and Agriculture, and, in Ecuador, the National Council on Social Participation.ResultsPesticide poisonings were more widespread than existing passive surveillance systems would suggest. More diversified, moderately developed agricultural systems had lower pesticide use and better child nutrition. Greater understanding among women of crop management options and more equal household gender relations were associated with reduced farm pesticide use and household pesticide exposure. Involvement in more organic agriculture was associated with greater household food security and food sovereignty. Markets for safer produce supported efforts by smallholder farmers to reduce hazardous pesticide use.Participatory interventions included: promoting greater access to alternative methods and inputs in a store co-sponsored by the municipality; producing less harmful inputs such as compost by women farmers; strengthening farmer organizations around healthier and more sustainable agriculture; marketing safer produce among social sectors; empowering farmers to act as social monitors; and using social monitoring results to inform decision makers. Uptake by policy makers has included: the Ecuadorian Ministry of Health rolling out pesticide poisoning surveillance modeled on our system; the Ecuadorian Association of Municipalities holding a national virtual forum on healthier agriculture; and the Ecuadorian Ministry of Agriculture promulgating restrictions on highly hazardous pesticides in June 2010.ConclusionWork with multiple actors is needed to shift agriculture towards greater sustainability and human health, particularly for vulnerable smallholders.