OBJECTIVE: This study evaluated whether serious bacterial infections are more frequent at family practices with lower antibiotic prescribing rates. DESIGN: Cohort study. SETTING: 706 UK family practices in the Clinical Practice Research Datalink from 2002 to 2017. PARTICIPANTS: 10.1 million registered patients with 69.3 million patient-years' follow-up. EXPOSURES: All antibiotic prescriptions, subgroups of acute and repeat antibiotic prescriptions, and proportion of antibiotic prescriptions associated with specific-coded indications. MAIN OUTCOME MEASURES: First episodes of serious bacterial infections. Poisson models were fitted adjusting for age group, gender, comorbidity, deprivation, region and calendar year, with random intercepts representing family practice-specific estimates. RESULTS: The age-standardised antibiotic prescribing rate per 1000 patient-years increased from 2002 (male 423; female 621) to 2012 (male 530; female 842) before declining to 2017 (male 449; female 753). The median family practice had an antibiotic prescribing rate of 648 per 1000 patient-years with 95% range for different practices of 430-1038 antibiotic prescriptions per 1000 patient-years. Specific coded indications were recorded for 58% of antibiotic prescriptions at the median family practice, the 95% range at different family practices was from 10% to 75%. There were 139 759 first episodes of serious bacterial infection. After adjusting for covariates and the proportion of coded consultations, there was no evidence that serious bacterial infections were lower at family practices with higher total antibiotic prescribing. The adjusted rate ratio for 20% higher total antibiotic prescribing was 1.03, (95% CI 1.00 to 1.06, p=0.074). CONCLUSIONS: We did not find population-level evidence that family practices with lower total antibiotic prescribing might have more frequent occurrence of serious bacterial infections overall. Improving the recording of infection episodes has potential to inform better antimicrobial stewardship in primary care.