OBJECTIVES: To investigate leftover antibiotics and their influence on self-medication with antibiotics (SMA) for Chinese children, and further explore the different influences of leftovers from two main sources: previous prescriptions and pharmaceutical purchases. DESIGN: A cross-sectional questionnaire study. SETTING: The participants were approached through kindergartens and primary schools as well as in vaccination clinics. PARTICIPANTS: A total of 9526 parents from three Chinese provinces whose children were aged 0-13 years completed the survey. OUTCOME MEASURES: The prevalence of keeping antibiotics at home for children and the proportion of leftover antibiotics from two main sources were measured by a self-administrated questionnaire. Logistic regression models were established to examine the association between keeping antibiotics at home and SMA for children, specifically the risks of leftovers from two main sources. RESULTS: Overall, 4580 (48.1%) reported keeping antibiotics at home for children. Among those who had leftovers, 2891 (63.1%) reported that their leftovers came from previous prescriptions and 1619 (35.3%) reported that their leftovers came from pharmaceutical purchases. Mothers, older age of child, higher household income, higher education level and medical background were significantly associated with keeping antibiotics at home. Keeping antibiotics at home was significantly associated with SMA for children (adjusted OR=4.91, 95% CI 3.84 to 6.28). Particularly, compared with parents who did not keep antibiotics at home, parents who kept leftover antibiotics from previous prescriptions and those whose leftovers came from pharmaceutical purchases were 3.80 (95% CI 2.89 to 5.00) and 6.45 (95% CI 4.89 to 8.51) times more likely to engage in SMA for children, respectively. CONCLUSIONS: Keeping antibiotics at home for children was pervasive in China. Most leftovers came from previous prescriptions, while those from pharmacies had a higher risk of SMA for children.