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Abstract Background There is considerable variation among physicians in inappropriate antibiotic prescribing, which is hypothesized to be attributable to diagnostic uncertainty and ineffective communication. The objective of this study was to evaluate whether clinical and communication skills are associated with antibiotic prescribing for upper respiratory infections and sinusitis. Methods A cohort study of 2,526 international medical graduates and 48,394 U.S. Medicare patients diagnosed by study physicians with an upper respiratory infection or sinusitis between July 2014 and November 2015 was conducted. Clinical and communication skills were measured by scores achieved on the Clinical Skills Assessment examination administered by the Educational Commission for Foreign Medical Graduates (ECFMG) as a requirement for entry into U.S residency programs. Medicare Part D data were used to determine whether patients were dispensed an antibiotic following an outpatient evaluation and management visit with the study physician. Physician age, sex, specialty and practice region were retrieved from the ECFMG databased and American Medical Association (AMA) Masterfile. Multivariate GEE logistic regression was used to evaluate the association between clinical and communication skills and antibiotic prescribing, adjusting for other physician and patient characteristics. Results Physicians prescribed an antibiotic in 71.1% of encounters in which a patient was diagnosed with sinusitis, and 50.5% of encounters for upper respiratory infections. Better interpersonal skills scores were associated with a significant reduction in the odds of antibiotic prescribing (OR per score decile 0.93, 95% CI 0.87–0.99), while greater proficiency in clinical skills and English proficiency were not. Female physicians, those practicing internal medicine compared to family medicine, those with citizenship from the US compared to all other countries, and those practicing in southern of the US were also more likely to prescribe potentially unnecessary antibiotics. Conclusions Based on this study, physicians with better interpersonal skills are less likely to prescribe antibiotics for acute sinusitis and upper respiratory infections. Future research should examine whether tailored interpersonal skills training to help physicians manage patient expectations for antibiotics could reduce unnecessary antibiotic prescribing.