OBJECTIVES: This study compared the osseointegrative potential of a novel injection molded zirconia dental implant (Neodent Zi ceramic implant, test) and a commercially available titanium implant (Neodent Alvim implant, control) in terms of histomorphometrically derived bone-to-implant contact (BIC), first bone-to-implant contact (fBIC), and the ratio of bone area to total area (BATA) around the implant. MATERIALS AND METHODS: A total of 36 implants, 18 per individual test device, were implanted in a split-mouth arrangement in either side of the edentulous and fully healed mandible of 6 minipigs. Histomorphometric analysis of BIC, fBIC, and BATA were performed 8 weeks post implantation and subjected to statistical non-inferiority testing. Surface characteristics of both implant types were compared in terms of contact angle, surface topography, and elemental composition. RESULTS: BIC, fBIC, and coronal BATA values of test and control implants were statistically comparable and non-inferior. BIC values of 77.8 ± 6.9% vs. 80.7 ± 6.9% (p = 0.095) were measured for the test and control groups. fBIC lingual values were - 238 ± 328 µm compared with - 414 ± 511 µm (p = 0.121) while buccal values were - 429 ± 648 µm and - 588 ± 550 µm (p = 0.230) for the test and control devices, respectively. BATA in the apical segment was significantly higher in the test group compared with the control group (67.2 ± 11.8% vs. 59.1 ± 11.4%) (p = 0.0103). Surface topographies of both implant types were comparable. Surface chemical analysis indicated the presence of carbonaceous adsorbates which correlated with a comparable and predominantly hydrophobic character of the implants. CONCLUSION: The results demonstrate that the investigated zirconia implants, when compared with a commercially available titanium implant, show equivalent and non-inferior bone integration, bone formation, and alveolar bone level maintenance. This qualifies the investigated zirconia implant as a potential candidate for clinical development. CLINICAL RELEVANCE: This study investigated the osseointegration of a novel zirconia 2-piece dental implant prototype intended for clinical development. With the aim of translating this prototype into clinical development preclinical models, procedures and materials within this study have been selected as close to clinical practice and human physiological conditions as possible.