Ibuprofen is a nonselective nonsteroidal antiinflammatory drug commonly prescribed for acute postsurgical and posttraumatic pain. However, little known is about the effect of this drug on osteoblasts. In this study, we aimed to investigate the effect of ibuprofen on cell proliferation, differentiation, antigenic profile, and phagocytic activity, in a human MG-63 osteosarcoma cell line, as a model of osteoblasts. Flow cytometry was used to study proliferation, antigenic profile, and phagocytic activity, and radioimmunoassay was used to determine osteocalcin synthesis as a cell differentiation marker. Our results showed that therapeutic doses of ibuprofen (5 and 25 μM) did not modify cell proliferation and osteocalcin synthesis in the MG-63 cellular line. However, treatment with a higher dose (25 μM) increased the expression of antigens CD21, CD44, CD80, CD86, and HLA-DR and decreased phagocytic activity. The results indicate that a therapeutic dose of ibuprofen has no adverse effects on growth of the osteoblast-like cells. Treatment with ibuprofen alone may produce some cell activation, which would explain the increase in expression of membrane markers and decrease in phagocytic capacity.