OBJECTIVES: There is a wide variation between European countries in antibiotic prescribing for patients in primary care with lower respiratory tract infection (LRTI) that is not explained by case mix and clinical factors alone. Variation in antibiotic prescribing that is not warranted by differences in illness and clinical presentation may increase selection of resistant organisms, contributing to the problem of antibiotic resistance. This study aimed to investigate clinicians' accounts of non-clinical factors that influence their antibiotic prescribing decision for patients with LRTI, to understand variation and identify opportunities for addressing possible unhelpful variation. DESIGN: Multicountry qualitative semistructured interview study, with data subjected to a five-stage analytic framework approach (familiarisation, developing a thematic framework from interview questions and emerging themes, indexing, charting and interpretation), and with interviewers commenting on preliminary analytic themes. SETTING: Primary care. PARTICIPANTS: Eighty primary care clinicians randomly selected from primary care research networks based in nine European cities. RESULTS: Clinicians' accounts identified non-clinical factors imposed by the healthcare system operating within specific regional primary care research networks, including patient access to antibiotics before consulting a doctor (Barcelona and Milan), systems to reduce patient expectations for antibiotics (Southampton and Antwerp) and lack of consistent treatment guidelines (Balatonfüred and Łódź). Secondly, accounts revealed factors related to specific characteristics of clinicians regardless of network (professional ethos, self-belief in decision-making and commitment to shared decision-making). CONCLUSIONS: Addressing healthcare system factors (eg, limiting patients' self-management with antibiotics before consulting in primary care, increased public awareness and provision of more consistent guidelines) may assist in reducing unhelpful variation in antibiotic prescribing. Promoting clinicians' receptivity to change, confidence in decision-making and readiness to invest in explaining prescribing decisions may also be beneficial. As factors were emphasised differently between networks, local flexibility in interventions is likely to maximise effectiveness.