Some evidence suggests a daily dose of bisphosphonates improves fixation of cementless metal implants by enhancing osseointegration. Because the necessity of daily administration may result in suboptimal adherence to therapy, single- dose administration is desirable. We examined whether a dose-equivalent single injection of the nitrogen-containing bisphosphonate ibandronate is as effective as a daily injection in improving the osseointegrated surface and enhancing periprosthetic bone mineralization (bone volume to tissue volume) of cementless metal implants. Uncoated titanium and hydroxyapatite-coated titanium implants were surgically inserted into the femoral medullary canal of 55 female Sprague Dawley rats. The animals were randomly assigned subcutaneous treatments with 25 microg/kg body weight ibandronate per day, a dose-equivalent single injection of 28 x 25 microg/kg body weight, or saline solution for control. Histomorphometric evaluation revealed an enhanced osseointegrated surface for hydroxyapatite-coated implants in both treatment groups, but only for daily injections for uncoated titanium implants. Bone volume to tissue volume was improved in both treatment groups. Our results suggest that an equivalent-dose single injection of ibandronate is as effective as a daily dose in improving osseointegration and stabilization of hydroxyapatite-coated titanium implants in this rat model.