Ceftriaxone, a broad-spectrum cephalosporin with a markedly extended half-life, was administered to 100 patients with 56 bone and 44 soft tissue infections. Sixty-eight received 1 g twice daily, and 32 received 2 g once daily intravenously. Overall, 91% had a satisfactory clinical response, with similar efficacies in both treatment regimens. In six patients, failure to achieve a cure correlated well with the development of resistance to ceftriaxone during therapy in Enterobacter and Pseudomonas species (two cases) and with superinfection with Bacteroides fragilis (four cases). In 41 patients, intravenous drug therapy was continued after discharge from the hospital. In this group, 1,093 patient-days of hospitalization were saved, amounting to $150,020 in cost savings. The prolonged half-life facilitated the administration of ceftriaxone in this setting.