During a 2-year period, 10 Portuguese hospitals located throughout the country studied antimicrobial susceptibilities of clinically relevant staphylococci and enterococci. Of more than 12,000 Staphylococcus aureus isolates tested, two main patterns were found, methicillin-sensitive organisms most of them resistant only to penicillin but a few to other antimicrobials and methicillin-resistant S. aureus (MRSA) strains (prevalence 48.2%) resistant to most of the antimicrobials tested and uniformly susceptible to vancomycin. Among coagulase-negative staphylococci (CNS), 71% of S. epidermidis (approximately 5,000 isolates tested) and 84% S. haemolyticus (approximately 1,000 isolates tested) were also resistant to methicillin as well as most other antimicrobials except vancomycin. Most of the 5,000 Enterococcus faecalis isolates tested were susceptible to ampicillin and vancomycin, in contrast to 650 E. faecium isolates, 70% of which were resistant to ampicillin and 20% to vancomycin and all other antibiotics. A high prevalence of aminoglycoside resistance occurred in both Enterococcus species. This survey showed that resistance profiles of staphylococci and enterococci hospital isolates have not changed in the last 5 years in Portugal, with the exception of the rise in vancomycin resistance in E. faecium. The high prevalence of methicillin resistance in S. aureus and in the CNS remains an issue of medical concern.