This systematic review examines the methods and results of recent studies reporting clinical criteria able to identify patients with Staphylococcus aureus bacteremia who are at very low risk of endocarditis. We searched PubMed, EMBASE, and the Cochrane Collaboration CENTRAL database for articles published after March 1994 using a combination of MeSH and free text search terms for S. aureus AND bacteremia AND endocarditis. Studies were included if they presented a combination of clinical and microbiological criteria with a negative likelihood ratio of ≤0.20 for endocarditis. We found 8 studies employing various criteria and reference standards whose criteria were associated with negative likelihood ratios between 0.00 and 0.19 (corresponding to 0%–5% risk of endocarditis at 20% background prevalence). The benefit of echocardiography for patients fulfilling these criteria is uncertain.