Abstract Introduction Antibiotic-resistant infections are the biggest threat to modern medicine. In 2019 there were 1.27 million deaths globally as a result of antibiotic resistance. Without a solution, estimates predict that by 2050 that number will be closer to 10 million people every year who are dying from previously treatable bacterial infections1. The end of the antibiotic era is a rising concern, as antimicrobial resistance continues to be recognised as a global health threat2. Promoting appropriate use and disposal of antibiotics is a key aspect of antibiotic amnesty campaigns, which work towards the bigger picture of reducing antimicrobial resistance (AMR)3. Studies that fill in the gaps in knowledge regarding the challenges and solutions to antibiotic amnesties are lacking. Aim To investigate the main enablers and barriers of antibiotic amnesty campaigns in community pharmacies in Huddersfield, Bradford, Leeds and Sheffield and to identify the most commonly returned antibiotics. Methods This study required and received ethics approval from the University of Huddersfield. A semi-structured interview guide was developed and used to interview consenting community pharmacy staff located in Huddersfield, Bradford, Leeds and Sheffield. Data was collected over a designated 5-week period in January and February 2023 by audio recorded interviews either over Microsoft Teams or face-to-face. Data was groups into themes. All recordings were deleted once transcribed. Results There were 20 interviews conducted, averaging 20 minutes in duration. Participants included 10 pharmacists, 5 pharmacy technicians and 5 medicine counter staff which were evenly divided between age groups 18-39 (n=10) and 40-59 (n=10). The main themes extracted at analysis included; factors enabling campaigns, antibiotic challenges relating to unnecessary use, education enabling amnesty campaigns, and raising awareness to maximise return of unwanted antibiotics. The sub-themes from all three staff groups which suggested enablers for antibiotic amnesty campaigns were, counselling patients, promotional resources and personal approach. The barriers were lack of educating staff, antibiotic misuse by patients, fear of re-infection (saving spare), minor ailments service, inappropriate prescribing and lack of patient education. The most frequently returned antibiotics were penicillins, especially amoxicillin. Discussion/Conclusion The main enablers of antibiotic amnesties are effective counselling and successful use of promotional resources. The main barriers were lack of patient education and lack of staff education. These barriers can be tackled with provision of sufficient education, training and knowledge for patients. Staff could increase the chances of success with antibiotic amnesty campaigns in the future by addressing these issues. Amoxicillin was the most returned antibiotic. It is used to treat many types of bacterial infections, especially respiratory. Shorter courses, back-up prescriptions or alternative treatment options should be considered to reduce leftovers. Study limitations include accounting for ethnicity. Future studies should include more medium and large chain pharmacies over a wider geographical area.