Proximal bone resorption around the femoral stem is one of the major complications of cementless total hip arthroplasty (THA). The potential complications resulting from proximal bone resorption include femoral fracture and late stem loosening. The purpose of this study was to evaluate the effects of cyclic therapy with etidronate on periprosthetic bone mineral density (BMD) after cementless THA. Fifty-two patients who had undergone cementless THA were randomized for this study. Group A consisted of 30 hips in 29 patients without osteoactive drugs. Group B consisted of 23 hips in 23 patients with cyclic therapy with etidronate (i.e., 400 mg/day of oral etidronate for 2 weeks followed by 12 weeks of 500 mg/day of calcium lactate and repeated every 14 weeks), one of whom was excluded from the study because of side effects attributed to the drug. Periprosthetic BMD in seven regions of interest based on the zones of Gruen et al. (Clin. Orthop. 141 (1979), 17-27) was measured with dual energy X-ray absorptiometry (DXA) at 3 weeks, 6 months, and 12 months postoperatively. The postoperative decreases of BMD in group B were significantly lower than those in group A in zones 1 and 7 (P < 0.05 and P < 0.05, respectively) at 6 months and in zones 1, 2, 6, and 7 (P < 0.05, P < 0.05, P < 0.05, and P < 0.001, respectively) at 12 months. The BMD change appeared to be stabilized at 6 months in all zones in group B, while in group A there was a progressive decrease of average BMD (6.1%) in zone 7 between 6 months and 12 months. These findings suggested that cyclic therapy with etidronate may help to reduce the resorptive changes in the proximal part of the femur after cementless THA. Further follow-up study with larger populations will be required to define the potential efficacy of intermittent cyclic etidronate therapy on postoperative bone loss.