A central dental implant success criterion is the marginal bone response as measured longitudinally. Factors that influence marginal bone changes include osseous and soft tissue architecture, occlusal loading factors, implant position, implant design, and inflammatory processes. The evolution of implant design is multifactorial and includes the implant-abutment interface geometries. The primary objective of this study was to compare the proximal marginal bone changes following placement and loading of internal conus design implants (ICI) and external hex design implants (EXI) used in the treatment of posterior partial edentulism. Among 45 enrolled participants, 39 were treated with 47 ICI or 46 EXI implants using a one-stage implant protocol. Prosthetic restoration was completed after 12 weeks using stock titanium abutments and all-ceramic crowns. Follow-up visits including clinical and radiographic examinations were performed 6 months after permanent restoration and then annually for 3 years. Marginal bone level changes, papilla index scores, condition of the peri-implant mucosa, presence of complications, and participant satisfaction were evaluated. The mean marginal bone level change from implant placement to 3 years was -0.25 ± 0.60 mm and -0.5 ± 0.93 mm for ICI and EXI implants, respectively. The change recorded from permanent restoration to 3 years was a gain of 0.31 ± 0.41 mm versus 0.04 ± 0.51 mm for ICI and EXI implants, respectively (P .05). In the evaluation of interproximal soft tissue 3 years after permanent restoration, 80% of mandibular and 66% of maxillary interproximal ICI sites received papilla scores of 2 and 3, compared with 50% of mandibular and 60% of maxillary interproximal EXI sites. No significant differences in plaque or bleeding scores were recorded. Abutment/healing abutment complications were recorded for 11 EXI versus 1 ICI participant. The vast majority (> 90%) of participants stated they were satisfied or very satisfied with their implant prosthesis and rated function and esthetics highly for both implant types after 3 years in function. Modestly greater marginal bone loss occurred at EXI implants. Further, more positive papilla scores were found between adjacent ICI implants than between adjacent EXI implants. EXI implants displayed more abutment complications than the ICI implants. The implant-abutment interface design may contribute to therapeutic outcome differences. Replacement of missing posterior teeth with unsplinted implants was successful at the implant level and as reported by the participant.