As a ceramic, silicon nitride (Si3N4) has been suggested as a biocompatible material in contact with bone. In another configuration, as a low pressure chemically vapor deposited (LPCVD) thin film, Si3N4 can also be used as the sensitive material in certain biosensor applications. With the latter in mind, the biocompatibility of such films was investigated after them being modified with silane based self-assembled monolayers (SAMs) bearing functional end groups of methyl (CH3), primary amine (NH2), and carboxyl (COOH) respectively. The SAM surface modifications provided a wide range of physiochemical properties including hydrophobic (CH3), hydrophilic (bare Si3N4), positively (NH2) and negatively charged (COOH). Specifically the cell adhesion and proliferation, as well as the levels of alkaline phosphatase activity and osteocalcin, have been evaluated using the human osteoblast-like MG-63 cell line. It was observed that attachment and spreading was pronounced on NH2 while suppressed on CH3. With time the cells grew to confluence on all chemistries, and the levels of osteocalcin normalized to total protein content varied as CH3 > Si3N4 > COOH > NH2, but without significant differences. The highest spontaneous alkaline phosphatase activity was observed from cells grown on Si3N4 substrata.