Fifty-two patients enrolled in the Septopal study of infected nonunions were prospectively examined in a randomized, controlled, closed study. Patients were divided into two groups. Group 1 consisted of 24 patients treated with debridement and intravenous antibiotics for four weeks. Group 2 consisted of 28 patients treated with debridement, gentamicin-polymethylmethacrylate (Septopal) beads, and perioperative broad-spectrum parenteral antibiotics. Both groups were treated with similar methods for reconstruction of the nonunions. The demographics of the two groups were similar. The average patient age in Group 1 was 38.4 years, and in Group 2, 37.1 years. Group 1 included 21 men and three women and Group 2, 23 men and five women. The nonunions in both groups ranged from simple hypertrophic nonunions to atrophic unions to segmental defects. The end results were good in both groups. Twenty patients in Group 1 and 25 patients in Group 2 had their infections successfully arrested (83.3% and 89.3%, respectively). Nonunions were successfully healed in the two groups, with similar results (Group 1, 83.3%; Group 2, 85.7%). Infected nonunions responded equally well to either systemic treatment with long-term intravenous antibiotics or local treatment with gentamicin-polymethylmethacrylate beads.