Abstract: Bacterial endocarditis due to Serratia species typically involves left-sided heart valves and is associated with a high mortality rate. We describe a case of polymicrobial Serratia marcescens and Streptococcus mitis tricuspid valve infection successfully treated with medical therapy. A review of the literature revealed 73 cases of endocarditis due to Serratia species, including 16 cases (21.9%) with mixed infection. Endocarditis due to Serratia is most frequently seen among injection drug users, and most cases (73.2%) involve left-sided valves. There is a high mortality rate (58.3%) overall, and risk factors for death included involvement of left-sided valves (odds ratio, 19.5; 95% CI, 3.0–126.4; P = 0.002) and evidence of metastatic infection (odds ratio, 8.5; 95% CI, 1.1–64.4; P = 0.039). Polymicrobial endocarditis involving Serratia species also has a high mortality rate (60%) and a predilection for left-sided valves (75%). Whereas our case recovered with a 6-week combination antibiotic regimen, the optimal treatment strategy is unknown.