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Purpose: The goal of this investigation was to define time-dependent peri-implant tissue changes at implants with different abutment interface designs., Materials and Methods: Participants requiring replacement of single maxillary anterior and first premolar teeth were recruited and treated under an institutional review board (IRB)-approved protocol. Implants, titanium abutments, and provisional crowns were placed in healed ridges 5 months following preservation after tooth extraction with recombinant human bone morphogenetic protein-2 (rhBMP-2). Twelve weeks later, permanent crowns were placed on patient-specific abutments and evaluated at 6, 12, and 36 months following implant placement. Clinical and radiographic assessments of abutments and crowns, peri-implant mucosa, and marginal bone levels were recorded., Results: The 3-year assessment included 45 conical interface (CI), 34 flat-to-flat interface (FI), and 32 platform-switched interface (PS) implants in 111 participants. At 3 years, the mean marginal bone level (MBL) change at CI, FI, and PS implants was -0.12, -1.02, and -1.04 mm, respectively (P = .014). "Zero" MBL loss or gain was measured over the 3-year period at 72.1% CI, 3.0% FI, and 16.6% PS implants. There was a minor change (0.0 to 0.3 mm) in peri-implant mucosal zenith positions over time and between groups. Eighty percent of CI implants, 61% of FI implants, and 84% of PS implants were observed to have a clinically stable peri-implant mucosal zenith position with less than 0.5 mm of measured recession. Over the 36-month period, there were no significant changes in the location of mesial or distal papilla in any group., Conclusion: Significant differences in MBLs were observed at different implant interfaces. Conical implant interfaces, but not flat-to-flat or platform-switched implant interfaces, were associated with no MBL changes over 3 years. Peri-implant mucosal stability was generally observed. The relationship of marginal bone responses and peri-implant mucosal stability requires further evaluation.