Purpose: To compare the effect of ceramic and metal implant materials on the expression pattern of inflammatory cytokines in peri-implant soft tissue. Materials and Methods: This split-mouth study included patients who received dental implants. In each patient, four different materials were used for the implant cover screws: the ceramic material titanium niobium oxynitride ([Ti,Nb]ON) with plasma-chemical oxidation treatment, (Ti,Nb)ON, a titanium-tantalum alloy, and tantalum. Biopsy specimens of peri-implant tissue were harvested at reentry, 4 months after the initial surgery. Immunohistochemical staining was performed for tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Results: Six patients received a total of 24 dental implants with the four different types of implant cover screws. Quantitative analysis of TNF-α and IL-6 expression showed the lowest expression of IL-6 (1.5; interquartile range, 0 to 8.5) and TNF-α (4.8; interquartile range, 3.5 to 7.5) in tissue adjacent to the (Ti,Nb)ON layer. In comparison to the metal surfaces, the expression of both cytokines was significantly lower (P = .01 and P = .03). Conclusions: The lowest levels of cytokine expression were observed in tissue adjacent to the ceramic (Ti,Nb)ON coating with plasma-chemical oxidation. Based on the results of this study, this ceramic layer shows promise as a biocompatible material, and further study is warranted. Keywords: biocompatibility, cytokine, dental implant, metal-ceramic bonding, peri-implantitis, tantalum, titanium alloy