Background:Over-prescription of antibiotics is prevalent all over the world, contributing to the development of antibiotic resistance. The importance of understanding how physicians prescribe antibiotics is increasingly highlighted for the purpose of promoting good practice. This study aimed to identify factors that shape the antibiotic prescribing behaviors of physicians in primary care based on the theory of planned behavior (TPB). Methods:Data were collected from 503 prescribers within 65 primary care facilities in Hubei, tapping into four behavioral aspects leading to antibiotic prescribing based on TPB, namely, attitudes (the degree to which a prescriber is in favor of the use of antibiotics), subjective norms (perceived social pressure to which a prescriber is subject in relation to antibiotic prescriptions), perceived control of behaviors (how easy a prescriber feels in making a rational decision on antibiotic prescriptions) and intentions (the degree to which a prescriber is willing to prescribe antibiotics). A total of 440,268 prescriptions were audited to assess physician antibiotic prescribing practices. The four behavioral constructs were further linked with physician's actual use of antibiotics using structural equation modelling (SEM) based on TPB. Results:On average, 40.54% (SD = 20.82%) of the outpatient encounters resulted in a prescription for an antibiotic given by the participants and 9.81% (SD = 10.18%) of the patients were given two or more antibiotics. The participants showing a more favorable attitude toward antibiotics had a higher intention to prescribe antibiotics (β = 0.226, p < 0.001) and a lower intention to reduce antibiotic use (β = - 0.211, p < 0.001). Those who perceived lower social pressure (β = 0.113, p = 0.030) and higher control over prescribing behaviors (β = 0.113, p = 0.037) reported a higher intention to reduce the use of antibiotics. However, such intention did not translate into prescribing practice (p > 0.05), although stronger perceived behavioral control was directly linked with lower antibiotic prescriptions (β = - 0.110, p = 0.019). Weaker perceived behavioral control was evident in the participants who showed a less favorable attitude toward antibiotics (β = 0.128, p = 0.001). Conclusion:Antibiotic prescribing practice is not under the volitional control of prescribers in primary care in China. Their rational prescribing practice is likely to be jeopardized by perceived weak control over prescribing behaviors.