BackgroundIn March 2018, NHS England published guidance for clinical commissioning groups (CCGs) to encourage implementation of policy to reduce primary care prescriptions of over-the-counter medications, including simple analgesia.AimTo investigate the impact of guidance publication on prescribing rates of simple analgesia (oral paracetamol, oral ibuprofen, and topical non-steroidal anti-inflammatory drugs) in primary care; CCG guidance implementation intentions; and whether the guidance has created health inequality based on socioeconomic status.Design and settingInterrupted time series analysis of primary care prescribing data in England.MethodPractice-level prescribing data from January 2015 to March 2019 were obtained from NHS Digital. Interrupted time series analyses were used to assess the association of guidance publication with prescribing rates. The association between practice-level prescribing rates and Index of Multiple Deprivation scores before and after publication was quantified using multivariable Poisson regression. Freedom of information requests were submitted to all CCGs.ResultsThere was a statistically significant 4.4% reduction in prescribing of simple analgesia following guidance publication (adjusted incidence rate ratio 0.96, 95% CI = 0.92 to 0.99, P = 0.027), adjusting for underlying time trend and seasonality. There was considerable diversity across CCGs in whether or how they chose to implement the guidance. Practice-level prescribing rates were greater in more deprived areas.ConclusionGuidance publication was associated with a small reduction in the prescribing rates of simple analgesia across England, without evidence of creating additional health inequality. Careful implementation by CCGs would be required to optimise cost saving to the NHS.