PURPOSE: The emergence of antimicrobial resistance has led to increasing efforts to reduce unnecessary use of antibiotics in primary care, but potential hazards from bacterial infection continue to cause concern. This study investigated how primary care prescribers perceive risk and safety concerns associated with reduced antibiotic prescribing. METHODS: Qualitative study using semistructured interviews conducted with primary care prescribers from 10 general practices in an urban area and a shire town in England. A thematic analysis was conducted. RESULTS: Thirty participants were recruited, including twenty-three general practitioners, five nurses and two pharmacists. Three main themes were identified: risk assessment, balancing treatment risks and negotiating decisions and risks. Respondents indicated that their decisions were grounded in clinical risk assessment, but this was informed by different approaches to antibiotic use, with most leaning towards reduced prescribing. Prescribers' perceptions of risk included the consequences of both inappropriate prescribing and inappropriate withholding of antibiotics. Sepsis was viewed as the most concerning potential outcome of non-prescribing, leading to possible patient harm and potential litigation. Risks of antibiotic prescribing included antibiotic resistant and Clostridium difficile infections, as well as side effects, such as rashes, that might lead to possible mislabelling as antibiotic allergy. Prescribers elicited patient preferences for use or avoidance of antibiotics to inform management strategies, which included educational advice, advice on self-management including warning signs, use of delayed prescriptions and safety netting. CONCLUSIONS: Attitudes towards antibiotic prescribing are evolving, with reduced antibiotic prescribing now being approached more systematically. The safety trade-offs associated with either use or non-use of antibiotics present difficulties especially when prescribing decisions are inconsistent with patients' expectations.