The efficacy of teicoplanin, a glycopeptide antibiotic, in endocarditis is controversial, with differences observed in the efficacies of the regimens used in clinical trials in the USA and Europe. This retrospective study examined the outcomes, efficacy and safety of mono- and combination antibiotic therapy using teicoplanin, particularly in cases of Staphylococcus aureus endocarditis. A total of 115 patients, typically mixed endocarditis patients intolerant of previous antibiotic treatment, was enrolled at 29 centres throughout Europe. Combination therapy was more successful than monotherapy for treating native valve endocarditis (NVE) (93 vs. 85%, p > 0.05, NS) and for treating S. aureus NVE (84 vs. 50%, p > 0.05). Efficacies for prosthetic valve endocarditis (PVE) were similar (75 vs. 79%), while combination therapy was more successful in S. aureus PVE (100 vs. 67%) though the number of such patients was small (NS). Adverse events were reported by 24% of patients, with 19% probably or possibly related to teicoplanin. In 9% of cases the adverse event led to the termination of therapy. Teicoplanin was judged to be efficacious in mono- or combination therapy in streptococcal endocarditis, though augmentation with an aminoglycoside is recommended. The efficacy of teicoplanin demonstrated in enterococcal endocarditis represents a major therapeutic advance.