To determine the effectiveness of live attenuated influenza vaccine (LAIV) in reducing amoxicillin prescribing in preschool children in primary care. We used The Health Improvement Network (THIN), a large primary care database from the United Kingdom. We included children aged 2 to 4 years old at the start of either the 2013/14 or the 2014/15 winter season, with at least one amoxicillin prescription between September and May, irrespective of LAIV vaccination status. We used the self-controlled case series method to estimate influenza vaccine effectiveness (VE). The total study sample included 33 137 children from 378 general practices during the two winter seasons. Of these children, 43.4% with at least one amoxicillin prescription had been vaccinated. The rate of amoxicillin prescribing was significantly reduced during periods of influenza vaccine immunity. The associated VE for amoxicillin prescribing was 12.8% (95% CI 6.9%, 18.3%) in 2013/14 and 14.5% (9.6%, 19.2%) in 2014/15. Given a VE of 14.5%, we estimated that amoxicillin prescribing could have been reduced by 5.6% if LAIV uptake in children aged 2-4 years increased to 50% in the 2014/15 winter season. Influenza vaccination of young children may contribute to a reduction in the prescribing of amoxicillin, one of the most commonly prescribed antibiotics in primary care. Further studies are required to confirm the size of the effect.