The quality and quantity of primary care prescribing represents a fundamental determinant of the clinical and cost-effectiveness of the UK NHS. The aim of this study was to determine the ‘supply’ factors that affect primary care prescribing, controlling for ‘demand’ factors and consider the implications for clinical commissioning groups (CCGs). A detailed regression analysis was undertaken of prescribing in six therapeutic areas to determine differences in prescribing across primary care trusts (PCTs) in England. Results indicate that there are large unexplained variations in primary care prescribing. With the disbanding of the PCTs, and budgets moving to general practitioners (GPs), the role of efficiently and effectively managing prescribing will fall to GP commissioners. Therefore, mechanisms need to be put in place now to ensure that GPs are able to monitor their prescribing and reduce unnecessary drug usage, and further research into the reasons for variations in prescribing needs to be conducted at the CCG level.