Infective endocarditis (IE) is the bacterial or fungal infection of heart valves with an incidence of 1.5 to 11.6 per 100,000 people per year in Western countries. Left-sided IE (LSIE) can be managed medically with antimicrobial therapy alone, or surgically through valve repair or replacement with additional antimicrobial therapy guided by North American and European guidelines. Several multicenter studies have identified predictors of mortality in patients with IE. However, these consisted of mixed populations of medically and surgically treated patients with heterogenous healthcare delivery. At present, therefore, a knowledge gap exists on the predictors of short- and long-term outcomes in medically treated patients with IE. This information is important for identifying patients that are more likely to benefit from medical treatment versus surgical valve repair/replacement, as current Society guidelines have provided minimal guidance on this issue. The aim of this study was to provide a comprehensive analysis of medically treated isolated LSIE in a single tertiary care center over a 12-year period. Specifically, we sought to identify patient characteristics that were associated with acceptable outcomes from medical (i.e. never surgical) treatment. We hypothesized that certain patient and/or IE valvular characteristics would predict poor outcomes with medical only therapy.