OBJECTIVE: To qualitatively assess the effects of a multi-modal school-based water, sanitation and hygiene (WASH) intervention on handwashing behaviour among primary students in North Western (NW) Tanzania. DESIGN: The study was a qualitative assessment of barriers and facilitators to handwashing among students attending primary schools participating in the Mikono Safi Trial (Kiswahili for 'Clean Hands), a cluster-randomised trial assessing the impact of a school-based WASH intervention on selected soil transmitted helminth infections. Data collection methods included in-depth interviews with teachers, focus group discussions and friendship pair interviews with students collected between April and October 2018. The Capability-Opportunity-Motivation and Behaviour model was used to inform data collection and analysis. SETTING: The study was conducted in four purposively selected intervention schools in three districts of Kagera region, NW Tanzania (Bukoba urban, Bukoba rural and Muleba districts). PARTICIPANTS: Participants comprised 16 purposively selected teachers aged between 23 and 52 years and 100 students aged 7-15 years RESULTS: The Mikono Safi intervention increased students' reported capability and motivation to wash their hands with soap at key times, particularly after visiting the toilet. Improvements in students' handwashing knowledge and skills were reported by both teachers and students, and motivation for handwashing was enhanced by emotional drivers such as disgust, fear and nurture. Newly established handwashing stations improved the physical opportunity to wash hands, although the availability of water and the provision of soap was not always consistent (eg, due to internal organisational shortcomings or during the dry season). Students and teachers were actively engaged in intervention implementation which created a school community that valued and supported improved hand hygiene. CONCLUSION: The intervention was successful in improving capability and motivation for handwashing. Handwashing opportunity was also greatly improved, although the supply with water and soap was sometimes interrupted, calling for much stronger multi-sectoral collaboration to improve access to water at schools. TRIAL REGISTRATION NUMBER: ISRCTN45013173; Pre-results.