The effects of a short course of a COX‐2 inhibitor on bone healing when the drug is discontinued are unknown. We examined the effects of rofecoxib on bone ingrowth over a 6‐week period using a well‐defined animal model. The Bone Harvest Chamber was implanted bilaterally in mature rabbits. After osseointegration of the chamber, the following treatments were given for 6 weeks each, followed by a harvest in each case: control‐no drug; oral rofecoxib (12.5 mg/day) for the first 2 of 6 weeks; washout period‐no drug; oral rofecoxib for the last 2 of 6 weeks; washout period‐no drug; rofecoxib given continuously for all 6 weeks. Harvested specimens were snap‐frozen, cut into serial 6‐μm sections, and stained with hematoxylin and eosin and alkaline phosphatase (osteoblast marker), and processed using immunohistochemistry to identify the vitronectin receptor (osteoclast‐like cells). Rofecoxib given continuously for 6 weeks yielded statistically less bone ingrowth compared to the control treatment. Rofecoxib given during the initial or final 2 weeks of a 6‐week treatment did not appear to interfere with bone ingrowth. This suggests that the effects of COX‐2 inhibitors on bone are less profound when the drug is administered for a short period of time. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 279–287, 2005