Antibiotic use is a modifiable driver of antibiotic resistance. In many circumstances, antibiotic use is overly broad or unnecessary. We systematically assessed factors associated with antibiotic prescribing for respiratory tract infections (RTI). Studies were included if they used actual (not self-reported or intended) prescribing data, assessed factors associated with antibiotic prescribing for RTIs, and performed multivariable analysis of associations. We searched Medline, Embase, and International Pharmaceutical Abstracts using keyword and MeSH (medical subject headings) search terms. Two authors reviewed each abstract and independently appraised all included texts. Data on factors affecting antibiotic prescribing were extracted. Our searches retrieved a total of 2,848 abstracts, with 97 included in full-text review and 28 meeting full inclusion criteria. Compared to other factors, diagnosis of acute bronchitis was associated with increased antibiotic prescribing (range of adjusted odds ratios [aOR], 1.56 to 15.9). Features on physical exam, such as fever, purulent sputum, abnormal respiratory exam, and tonsillar exudate, were also associated with higher odds of antibiotic prescribing. Patient desire for an antibiotic was not associated or was modestly associated with prescription (range of aORs, 0.61 to 9.87), in contrast to physician perception of patient desire for antibiotics, which showed a stronger association (range of aORs, 2.11 to 23.3). Physician's perception of patient desire for antibiotics was strongly associated with antibiotic prescribing. Antimicrobial stewardship programs should continue to expand in the outpatient setting and should emphasize clear and direct communication between patients and physicians, as well as signs and symptoms that do and do not predict bacterial etiology of upper respiratory tract infections.T he rapid and ongoing spread of antimicrobial-resistant organisms threatens our ability to successfully treat a growing number of infectious diseases (1, 2). It is well established that antibiotic use is a significant, and modifiable, driver of antibiotic resistance (3-5), and that antibiotics are often misused (6). In settings where a prescription is required to access antibiotics, the prescriber-patient encounter is a logical target for improving appropriate use.Despite the importance of the topic, there is no existing systematic review to identify drivers of antibiotic prescribing from real prescription data. A narrative review of factors influencing antibiotic prescribing highlighted the multiple sources of influence affecting a potential prescribing encounter, including factors related to the prescribing physician (e.g., fear of failure, diagnostic uncertainty, or inadequate training), the patient (e.g., a high-risk or vulnerable patient history), and the environment (e.g., regulation of pharmaceutical prescribing and dispensing and lack of resources for etiological diagnosis) (7). Another study systematically reviewed reasons for inappropriate antibiotic prescriptions, f...