Purpose: Bacteremia with Staphylococcus aureus (SAB) is a serious clinical condition and is associated with a high mortality, ranging from 20 to 40 %. Different trials from tertiary referral hospitals demonstrate that infectious disease consultation and adherence to standard of care indicators reduce the high mortality. Data from <250-bed general hospitals are lacking in this context. Methods: Patient cases at a community 200-bed general hospital with documented SAB were retrospectively analyzed from January 2010 to March 2013 regarding defined standard of care indicators. In April 2013, an antibiotic stewardship bundle approach was implemented targeting SAB. Follow-up was available until December 2013. Adherence to the different components of the bundle was analyzed. Results: There were 64 cases of SAB reported. After exclusion of five cases, 39 cases were included in the pre-intervention period and 20 patients in the post-intervention period. Mean average bundle adherence increased from a baseline score of 0.8-3.7 (p < 0.001) in the post-intervention period, whereas in-hospital mortality decreased significantly (44 vs. 10 %, p < 0.001) despite or even because the absolute number of detected cases of SAB increased substantially after the intervention was initiated. Conclusion: Although we were unable to identify whether the bundle, one of its components, or procedural improvements are responsible for the success of the intervention, our study indicates that the applied approach is feasible and is accompanied by a significant reduction of in-hospital mortality in the secondary care setting. The intervention may serve as a model for other hospitals with similar structures and baseline situations.