Background Postoperative migration of a joint prosthesis is related to the risk of late loosening. We have previously reported that oral treatment with clodronate reduced migration of the cemented NexGen total knee prosthesis during the first postoperative year, as measured by radiostereometry (RSA). Oral bisphosphonate treatment is sometimes unpleasant, and local treatment will enable higher local concentrations. We now report the results of local peroperative treatment with another bisphosphonate, ibandronate, with the same prosthesis. Methods This is a double-blind, randomized study of 50 patients using RSA with maximal total point motion (MTPM) as primary effect variable. 1 mg ibandronate (1 mL) or 1 mL saline was applied to the tibial bone surface 1 min before cementation. RSA examination was done on the first postoperative day, and at 6, 12, and 24 months. Results One ibandronate-treated patient died of unrelated causes, and I control patient refused to come for follow-up, leaving 24 patients in each group for analysis. There were no cases of aseptic loosening. By repeated measures ANOVA, migration (MTPM) was reduced by local application of ibandronate (p = 0.006). The effect was most pronounced at 6 months, with a reduction from 0.45 to 0.32 mm (95% CI for reduction: 0.04-0.21 mm). At 12 months, the migration from the postoperative examination was reduced from 0.47 to 0.36 mm (95 % CI for reduction: 0.02-0.20 mm). At 24 months, the reduction was from 0.47 to 0.40 mm (95% CI: -0.01-0.16 mm). Interpretation This is the first study to show improvement of prosthesis fixation by local pharmacological treatment in humans. The treatment appears to be safe, cheap, and easy to perform. However, the improvement in postoperative stability was not greater than with systemic clodronate treatment.