BACKGROUND Limited data exist on infective endocarditis (IE) due to Streptococcus milleri (Sm) or beta-hemolytic streptococci (BHS). Because BHS and Sm share some physiologic and pathogenic properties, we wondered whether IE caused by these streptococci might present similarities. METHODS Through a nationwide retrospective study in France, the medical and microbiologic charts of adults with definite Sm or BHS IE observed between January 1, 1991, and December 31, 1996, in university and general hospitals were reviewed. RESULTS Fifty-six patients had BHS IE (33 men and 23 women; median age, 59 years; range, 18-91 years) and 29 had Sm IE (18 men and 11 women; median age, 66 years; range, 37-97 years). The BHS group tended to have more underlying medical conditions (46%) and fewer previous cardiopathies (48%) than the Sm group (28% and 71%, respectively). Multivariate analysis showed that a longer median time of IE evolution before diagnosis and identification of the presumed portal of entry were independently associated with Sm IE (P<.01). Extracardiac complications were more frequent in the BHS group (55%) than in the Sm group (39%). Comparison of echocardiographic findings between the 2 groups did not establish any statistically significant difference. Thirty-six patients (64%) in the BHS group and 18 (62%) in the Sm group underwent valve replacement. Overall, mortality was 27% for the BHS group and 14% for the Sm group. For all patients, multivariate analysis retained older age as the only significant risk factor for death (P =.01). CONCLUSION Compared with Sm IE, BHS IE occurs in younger patients with more underlying diseases and fewer underlying cardiopathies and has a more aggressive presentation and evolution.