One approach for prosthetic vascular surgery is to continue antimicrobial prophylaxis while intravascular lines and catheters are in place. However this may give rise to antimicrobial resistance in the colonizing bacterial flora. We studied 37 patients undergoing vascular surgery, who received either co-amoxyclav for three days (group 1), ofloxacin plus metronidazole for three days (group 2) or for one day (group 3), respectively. Seventeen hospitalized patients not undergoing surgery or receiving antibiotics were studied as controls. In groups I and II there was a significant decline in susceptibility to cloxacillin (12.8% respectively 23.6%) and ofloxacin (0.5% and 85% respectively) in skin staphylococci. The results from group 3 were intermediate. Molecular typing showed that the patient's susceptible community-derived strains were replaced by genetically unrelated resistant strains, probably hospital derived. Long-term prophylaxis should be avoided as colonization occurs with resistant strains.