Understanding uptake of complex interventions is an increasingly prominent area of research. The interplay of macro (such as changing health policy), meso (re-organisation of professional work) and micro (rationalisation of clinical care) factors upon uptake of complex interventions has rarely been explored. This study focuses on how English General Practitioners and practice nurses make sense of a complex intervention for the management of osteoarthritis, using the macro–meso–micro contextual approach and Normalisation Process Theory (NPT), specifically the construct of coherence. It is embedded in a cluster RCT comprising four control practices and four intervention practices. In order to study sense-making by professionals introduction and planning meetings (N = 14) between researchers and the practices were observed. Three group interviews were carried out with 10 GPs and 5 practice nurses after they had received training in the intervention. Transcripts were thematically analysed before comparison with NPT constructs. We found that: first, most GPs and all nurses distinguished the intervention from current ways of working. Second, from the introduction meeting to the completion of the training the purpose of the intervention increased in clarity. Third, GPs varied in their understanding of their remit, while the practice nurses felt that the intervention builds on their holistic care approach. Fourth, the intervention was valued by practice nurses as it strengthened their expert status. GPs saw its value as work substitution, but felt that a positive conceptualisation of OA enhanced the consultation. When introducing new interventions in healthcare settings the interaction between macro, meso and micro factors, as well as the means of engaging new clinical practices and their sense-making by clinicians needs to be considered.