(1) Background: Long-term dental implant performance depends on the interaction between mechanical load distribution and peri-implant tissue response. The influence of implant configuration and vertical placement on marginal bone remodeling and early inflammatory signaling remains unclear. Therefore, the aim of this study was to compare crestally placed tissue-level (TL) and subcrestally placed bone-level (BL) implant configurations regarding marginal bone loss (MBL) and inflammatory biomarkers in the peri-implant crevicular fluid (PICF). (2) Methods: In this prospective randomized trial, 58 implants (29 TL, 29 BL) randomly allocated at the implant level were placed in 30 healthy patients; 42 implants (21 TL, 21 BL) in 23 patients were analysed. TL implants were placed at the crestal level, whereas BL implants were positioned 2 mm subcrestally and restored after 2 months using definitive transepithelial abutments (one-time abutment concept). MBL was assessed radiographically at prosthesis delivery, 6 months after loading and at the final follow-up (12–24 months after loading; mean 19.9 months). PICF was collected 6 months after loading to determine interleukin-1β (IL-1β) and matrix metalloproteinase-8 (MMP-8) levels by enzyme-linked immunosorbent assay (ELISA). Data were analysed with linear mixed-effects models accounting for clustering of implants within patients and for repeated measurements. (3) Results: At the final follow-up, mean MBL was 0.55 mm for TL and 0.29 mm for BL implants; the between-group difference in change (0.26 mm; 95% CI −0.01 to 0.53 mm) was not statistically significant (p = 0.058). No statistically significant differences were detected in IL-1β (p = 0.723) or MMP-8 (p = 0.777) concentrations, and neither biomarker was significantly associated with bone loss after adjustment. (4) Conclusions: Subcrestally placed BL implants restored with a one-abutment–one-time protocol showed numerically, but not significantly, smaller marginal bone loss than crestally placed TL implants, and the magnitude of the difference was of limited clinical relevance. Because the configurations differed in several respects, the results cannot be attributed to implant design alone.

(1) Background: Long-term dental implant performance depends on the interaction between mechanical load distribution and peri-implant tissue response. The influence of implant macro-design and vertical placement on early inflammatory signaling remains unclear. Therefore, the aim of this study is to compare tissue-level (TL) and bone-level (BL) implant configurations regarding marginal bone loss (MBL) and peri-implant inflammatory biomarkers. (2) Methods: In this prospective randomized trial, 23 healthy patients received 42 implants (21 TL, 21 BL). TL implants were placed at the crestal level, whereas BL implants were positioned 2 mm subcrestally and restored after 2 months using definitive transepithelial abutments (one-time abutment concept). MBL was assessed radiographically at prosthesis delivery, 1 year, and 2 years. Peri-implant crevicular fluid was collected at 1 year to determine IL-1β and MMP-8 levels by ELISA. (3) Results: At 2 years, mean MBL increase was significantly greater for TL than BL implants (0.55 vs. 0.29 mm; p < 0.05), with significant differences at medial (p = 0.0072) and distal (p = 0.0142) sites. BL remodeling remained within the protective 2-mm subcrestal bone. IL-1β and MMP-8 levels were higher in TL implants but without significant differences (p > 0.05). (4) Conclusions: Marginal bone remodeling appears to reflect physiological biomechanical adaptation rather than active inflammation. Subcrestal BL placement may provide a protective buffer against crestal bone loss without increasing local inflammatory activity.