Objectives Explore the impact of changes to commissioning introduced in England by the Health and Social Care Act 2012 (HSCA) on cervical screening activity in areas identified empirically as particularly affected organisationally by the reforms. Methods Qualitative followed by quantitative methods. Qualitative: semi-structured interviews (with NHS commissioners, managers, clinicians, senior administrative staff from Clinical Commissioning Groups (CCGs), local authorities, service providers), observations of commissioning meetings in two metropolitan areas of England. Quantitative: triple-difference analysis of national administrative data. Variability in the expected effects of HSCA on commissioning was measured by comparing CCGs working with one local authority with CCGs working with multiple local authorities. To control for unmeasured confounders, differential changes over time in cervical screening rates (among women, 25-64 years) between CCGs more and less likely to have been affected by HSCA commissioning organisational change were compared with another outcome - unassisted birth rates - largely unaffected by HSCA changes. Results Interviewees identified that cervical screening commissioning and provision was more complex and â €fragmented', with responsibilities less certain, following the HSCA. Interviewees predicted this would reduce cervical screening rates in some areas more than others. Quantitative findings supported these predictions. Areas where CCGs dealt with multiple local authorities experienced a larger decline in cervical screening rates (1.4%) than those dealing with one local authority (1.0%). Over the same period, unassisted deliveries decreased by 1.6% and 2.0%, respectively, in the two groups. Conclusions Arrangements for commissioning and delivering cervical screening were disrupted and made more complex by the HSCA. Areas most affected saw a greater decline in screening rates than others. The fact that this was identified qualitatively and then confirmed quantitatively strengthens this finding. The study suggests large-scale health system reforms may have unintended consequences, and that complex commissioning arrangements may be problematic.