The biocompatibility of three sol–gel bioactive glasses with SiO 2 as the main constituent (75, 72.5 and 70 mol%), identical CaO content (25 mol%), and without or with P 2O 5 as third constituent (0, 2.5 and 5 mol%), have been analyzed (S75, S72.5P2.5, and S70P5 glasses). These studies were performed on both untreated glasses and on glasses coated with a hydroxycarbonate apatite (HCA) layer formed in vitro by soaking 7 d in an acellular simulated body fluid. Cell attachment, spreading and proliferation were studied using neonatal rat calvaria osteoblasts. Cells attach to the three untreated glasses but show a higher efficiency on that with the higher phosphate content (S70P5). The formation of the HCA layer significantly enhances this process (1.7-fold). In all cases, attachment is followed by cell spreading on the surface of the materials, adopting the cells a flattened morphology and showing diverse anchoring cell projections. Mitotic activity has been detected on osteoblasts growing on the sol–gel glasses, being this process 2–4-fold higher when the apatite-like layer is already formed. Taking into account the results herein presented, these bioactive glasses can be considered biocompatible. In addition, their biocompatibility is greatly enhanced after induction of the formation of an HCA layer.