Purpose: To compare the influence of ultraviolet (UV) irradiation and cold atmospheric pressure plasma (CAP) treatment on surface structure, surface chemistry, cytocompatibility, and cell behavior on zirconia in vitro. Materials and Methods: Zirconia samples (TZ-3YSB-E) were treated by UV irradiation, oxygen plasma, or argon plasma for 12 minutes each and compared with the nontreated samples. Surface analysis was conducted using scanning electron microscopy, roughness analysis, and x-ray photoelectron spectroscopy. Cell proliferation, viability, and cell attachment as well as cytotoxicity were evaluated using MC3T3-E1 murine osteoblasts cultivated directly on the zirconia samples. Results: Surface structure and roughness were not affected by the surface treatments. CAP and UV irradiation significantly reduced organic material and increased the surface oxidation on the zirconia samples. Furthermore, CAP and UV treatment significantly decreased the contact angle on the zirconia samples, indicating superhydrophilicity. Cell attachment was significantly increased on oxygen plasma-treated zirconia samples compared with the nontreated samples at all times (P .001). After 24 and 48 hours, cell proliferation and viability (P .001) were significantly increased on oxygen plasma-treated samples in comparison with the nontreated, UV-treated, and argon plasma- treated samples. Neither UV nor CAP treatment led to cytotoxicity. Conclusion: In vitro, surface treatment by UV irradiation or CAP causes a significant reduction of organic material, increases the hydrophilicity of zirconia, and improves the conditions for osteoblasts. The results stipulate that treatment of zirconia surfaces with oxygen plasma may favor cell proliferation. Palabras clave: cold atmospheric pressure plasma, dental implant, implant surface, photofunctionalization, UV light, zirconia