The effect of perioperative administration of indomethacin on attachment strength and bone growth into porous-coated titanium implants was evaluated in the canine transcortical plug model. Various drug administration protocols simulating clinical use of indomethacin were studied. These included chronic treatment (starting 2 weeks prior to surgery), treatment immediately after surgery, and treatment 3, 6, 9, and 18 weeks following surgery. Indomethacin therapy was continued until sacrifice at 3, 6, 12, 18, or 24 postoperative weeks. Push-out testing was performed to determine the maximum bone-implant interface shear strength, and quantitative histologic analysis was used to determine percentage of bone ingrowth. When indomethacin was administered chronically or immediately after surgery, a statistically significant decrease in bone-implant interface attachment strength was seen at 3 postoperative weeks but not at later periods. No adverse effect was observed in any group after the 3-week period. Quantitative histologic analysis demonstrated no significant differences in percentage bone ingrowth among any of the treatment protocols at 3 or 6 weeks after surgery. No significant difference was observed between any of the groups at 18 or 24 weeks. The results of this study suggest that perioperative administration of indomethacin does not significantly affect attachment strength or bone ingrowth into porous-coated implants except at early periods, in which cases a transient decrease in attachment strength occurs.