Current Staphylococcus aureus bacteremia (SAB) practice guidelines stratify treatment duration according to the likelihood of complications and recommend transesophageal echocardiography (TEE) in all cases. The benefit of TEE in uncomplicated SAB has not been validated. We performed a retrospective analysis of TEE and transthoracic echocardiography (TTE) among hospitalized adults with SAB in 3 prior observational studies (2002-2003, 2005-2006, and 2008-2009). Echocardiograms were ordered at the attending physician's discretion. SAB cases were stratified into the following types: complicated (persistent bacteremia [duration ≥3 d], relapse, and/or secondary foci); device-associated (intracardiac prosthetic devices); suspected endocarditis (the presence of murmurs or emboli); and uncomplicated (bacteremia duration ≤2 d, no device and/or secondary foci). We encountered 960 SAB cases; 83 were excluded (57 death/transfer/discharge within 48 h; 19 contaminants/no treatment; 7 care withdrawn). TEE and TTE were performed within 0-28 days of SAB onset in 177 (20.2%) and 321 (36.6%) instances, respectively. TEE was positive (with signs of endocarditis) in 42/177 (23.7%) cases: 7/39 (17.9%) community associated and 35/138 (25.4%) health care associated. It was positive in 29/120 (24.2%) complicated, 3/11 (27.3%) device-associated, 9/15 (60.0%) suspected endocarditis, and 1/31 (3.2%) uncomplicated cases of SAB. TTE was positive in 25/321 (7.8%) cases of SAB, 1 was uncomplicated; it was negative in 20/30 (66.7%) TEE-positive cases. Follow-up of ≥100 days was possible in 282/361 (78.1%) uncomplicated SAB; many (46.8%) received ≤15 days of therapy. None of them had relapses or secondary foci.These findings suggest that echocardiography is dispensable in cases of uncomplicated community-associated and health care-associated SAB. It should be limited to subsets with clinical findings of endocarditis, persistence, intracardiac devices, secondary foci, and relapse. The cost effectiveness of TTE prior to TEE among these patients is unknown.