Antibiotic use and antimicrobial resistance was compared between Vilnius and Huddinge University hospitals. Drug use data were expressed in number of defined daily doses/100 bed-days; antimicrobial resistance were given as percentages of resistant isolates. Thirty-five and 48 different antibiotic drugs were used in Vilnius and Huddinge, respectively. The overall consumption of antibiotics was 15 DDD/100 bed-days in Vilnius and 43 DDD/100 bed-days in Huddinge. Benzylpenicillin, ampicillin, and aminoglycosides were the major antibiotics in Vilnius; beta-lactamase-resistant penicillins, cefalosporins, and quinolones in Huddinge. In Vilnius, gentamicin made up one-quarter of the use. Staphylococcus aureus and Gram-negative isolates from wounds and blood were more resistant to gentamicin in Vilnius. S. aureus was more often methicillin resistant in Vilnius than in Huddinge. There was no S. aureus-resistant to vancomycin in either hospital. The vancomycin-resistant enterococci made up from 4% to 10% in Vilnius hospital, but they were not detected in Huddinge hospital (0%). The majority of Streptococcus pneumoniae isolates were sensitive to benzylpenicillin in both hospitals. The higher resistance of microorganisms to some antibiotics in Vilnius may be explained by heavy use of few antibiotics. Lower level of hygiene procedures, sampling bias, and other methodological issues may also have contributed. Guidelines for antibiotic use and hygienic procedures are now under development in Vilnius.