Background Besides public awareness and specialist knowledge and training of physicians, their self-confidence plays a key role for clinical decision-making in the respective area. Objective This exploratory study investigated the influence of the discipline on differences in self-confidence in dealing with antibiotics and in the self-rated knowledge. Methods In 2015 the multi-institutional reconnaissance of practice with multiresistant bacteria (MR2) questionnaire containing items on antibiotic prescription and multiresistant pathogens was sent out to 1061 physicians working in departments for internal medicine, general surgery, gynecology and obstetrics and urology. In 2017 a similar MR2 survey was sent to 1268 specialist and assistant physicians in anesthesiology in Germany. Besides demographic data 4 items on self-confidence in the use of antibiotic treatment and 11 items concerning self-rated knowledge about rational antibiotic therapy and multiresistant pathogens were included in the present analysis. Logistic regression analysis, the chi(2)-test and the Kruskal-Wallis test were used for statistical analysis of the influence of the discipline on these items. Results The response rates were 43% (456 out of 1061) from the non-anesthetists and 56% (705 out of 1268) from the anesthetists. Of the non-anesthetists 44% and 57% of the anesthetists had had no advanced training on antibiotic stewardship during the year before the study. In the overall analysis anesthetists (mean +/- SD: 2.53 +/- 0.54) were significantly less self-confident about antibiotics than colleagues from other departments (internal medicine: 3.10 +/- 0.50, general surgery: 2.97 +/- 0.44, gynecology and obstetrics: 3.12 +/- 0.42 and urology: 3.15 +/- 0.44) in the unadjusted (all p<0.001) and adjusted comparison. The analysis of self-rated knowledge about rational antibiotic prescription showed similar results. Senior consultant status and advanced training in infectiology were significantly associated with self-confidence and self-rated knowledge about antibiotics. Conclusion Anesthetists showed significantly less self-confidence in dealing with antibiotics than colleagues from other disciplines. Advanced training on a rational prescription of antibiotics was associated with a greater self-confidence, so that the implementation of compulsory courses on rational antibiotic stewardship in the respective residency curriculum needs to be considered.