This paper examines data from the novel use of Lesson Study (LS), an internationally known strategy for professional development, to improve the teaching of students (11-14 years old) with moderate learning difficulties (MLD). The paper aims to use a systematic qualitative analytic approach to identify variations in LS practice in a development and research project with about 100 teachers across 30 schools in two LS phases. It also examines the extent to which the immediate context of undertaking the LSs relates to the LS practices and the outcomes for teachers and learners. Different data sources were used to examine the LS context, LS practices and outcomes. Analysis showed how teachers adapted the LS strategy to their particular subject areas, the needs of students identified with MLD and their teaching contexts, while mainly keeping to the expected LS procedures. Co-variation analysis showed how the degree to which contexts were supportive of LS could be related to student learning gains and teacher outcomes, but no mediating factors were identified. The conclusions indicate the importance of context for successful LS use. The findings are discussed in terms of possible mediating factors to better understand what is involved in quality and effective LS.