Hospital antibiotic management teams (AMTs) have been recommended, but, in France, their concrete implementation remains scarce and their effectiveness largely unevaluated. The objective of this investigation was to evaluate the appropriateness of antibiotic therapy (AT) for bloodstream infections (BSIs) at a 950-bed university teaching hospital, and assess the role of an AMT in improving it. A prospective analysis of all significant BSIs occurring outside of the intensive care unit (ICU) during an 18-month period was carried out. AT was deemed effective if at least one prescribed antibiotic was effective in vitro, and appropriate if it was consistent with local recommendations. Out of 574 BSIs, 512 were evaluated: 231 community-acquired, 206 nosocomial, and 75 healthcare-associated. For 219 (42.8%) BSIs, the AT initiated prior to AMT intervention proved to be effective and appropriate, inappropriate but effective in 136 (26.5%), and ineffective or absent in 157 (30.7%). In the multivariate analysis, hospital-acquired and other healthcare-associated BSIs, as well as catheter-borne (CB) infections, were associated with inappropriate or absent AT. A recommendation from the AMT was given and followed in 233 (94%) out of 249 BSIs requiring intervention. Initially, two-thirds of BSIs outside the ICU did not receive appropriate AT. Healthcare-associated BSIs should, therefore, be the priority target of AMTs.