Prophylactic antibiotic administration for selected major orthopaedic procedures is feasible with wide-spectrum antibiotics that can achieve high tissue levels. We studied the influence of tourniquet on the in vivo concentrations of ceftazidime and ceftriaxone in soft tissue and bone. Our study group consisted of 47 patients undergoing reconstructive operations of lower extremities. The effect of different time intervals between antibiotic administration and tourniquet inflation was examined. Our data suggest that the time interval resulting in the highest tissue concentrations is approximately 20 min between administration and tourniquet inflation.