Abstract Background Antimicrobial stewardship programmes are needed in long-term care facilities (LTCFs) to tackle antimicrobial resistance. We aimed to identify factors associated with antibiotic use in LTCFs. Such information would be useful to guide antimicrobial stewardship programmes. Method We conducted a systematic review of studies retrieved from PubMed, Cochrane Library, Embase, APA PsycArticles, APA PsycINFO, APA PsycTherapy, ScienceDirect and Web of Science. We included quantitative studies that investigated factors associated with antibiotic use (i.e., antibiotic prescribing by health professionals, administration by LTCF staff, or use by residents). Participants were LTCF residents, their family, and/or carers. We performed a qualitative narrative synthesis of the findings. Results Of the 7,591 screened records, we included 57 articles. Most studies used a longitudinal design ( n = 34/57), investigated resident-level ( n = 29/57) and/or facility-level factors ( n = 32/57), and fewer prescriber-level ones ( n = 8/57). Studies included two types of outcome: overall volume of antibiotic prescriptions ( n = 45/57), inappropriate antibiotic prescription ( n = 10/57); two included both types. Resident-level factors associated with a higher volume of antibiotic prescriptions included comorbidities (5 out of 8 studies which investigated this factor found a statistically significant association), history of infection ( n = 5/6), potential signs of infection (e.g., fever, n = 4/6), positive urine culture/dipstick results ( n = 3/4), indwelling urinary catheter ( n = 12/14), and resident/family request for antibiotics ( n = 1/1). At the facility-level, the volume of antibiotic prescriptions was positively associated with staff turnover ( n = 1/1) and prevalence of after-hours medical practitioner visits ( n = 1/1), and negatively associated with LTCF hiring an on-site coordinating physician ( n = 1/1). At the prescriber-level, higher antibiotic prescribing was associated with high prescription rate for antibiotics in the previous year ( n = 1/1). Conclusions Improving infection prevention and control, and diagnostic practices as part of antimicrobial stewardship programmes remain critical steps to reduce antibiotic prescribing in LTCFs. Once results confirmed by further studies, implementing institutional changes to limit staff turnover, ensure the presence of a professional accountable for the antimicrobial stewardship activities, and improve collaboration between LTCFs and external prescribers may contribute to reduce antibiotic prescribing.