A prospective, two-arm, open study assessing plasma exposure to teicoplanin with two different prophylactic regimens (Group A (n = 23), 800 mg pre-operatively versus Group B (n = 24), 400 mg pre-operatively plus two doses of 200 mg 24 h apart) was carried out in patients undergoing major vascular surgery. The intent was to define the feasibility and the possible advantages of the single pre-operative high dose in ensuring therapeutically effective plasma concentrations (>10 mg/L) of teicoplanin even during long-lasting operations. At the end of the intervention, mean teicoplanin concentrations (+/-S.D.) were 14.05 +/- 5.13 mg/L and 5.39 +/- 2.13 mg/L in Groups A and B, respectively. At 24 h, average teicoplanin levels were 5.10 +/- 1.25 mg/L and 2.08 +/- 0.73 mg/L in Groups A and B, respectively; at 48 h they declined to 2.86 +/- 0.70 mg/L in Group A, whereas they rose to 2.67 +/- 0.82 mg/L after administration of 2.63 +/- 0.51 mg/kg at 24 h in Group B. Single pre-operative high-dose teicoplanin may ensure effective plasma levels even in cases of very long-lasting operations (>8 h) with no need for intraoperative re-dosing and may enable more appropriate prophylactic exposure than that achievable with the same total dose given in three administrations 24 h apart.