Purpose: To compare the clinical and radiological outcomes of two implant designs with different prosthetic interfaces and neck configurations. Materials and methods: Thirty-four partially edentate patients randomly received at least one NobelActive implant (Nobel Biocare, Göteborg, Sweden) with back-tapered collar, internal conical connection and platform shifting design, and one NobelSpeedy implant (Nobel Biocare) with external hexagon and flat-to-flat implant-abutment interface according to a split-mouth design. Follow-up continued to 3 years post-loading. The primary outcome measures were the success rates of the implants and prostheses, and the occurrence of any surgical and prosthetic complications during the entire follow-up. Secondary outcome measures were: horizontal and vertical peri-implant marginal bone level (MBL) changes, resonance frequency analysis values at implant placement and loading (4 months), sulcus bleeding index (SBI) and plaque score (PS). Results: No drop-out occurred. No implants and prostheses failures were observed to the 3-year follow-up. MBL changes were statistically significant different with better results for the NobelActive implants for both horizontal and vertical measurements (P = 0.000). After 3 years post-loading, the NobelActive implants underwent a mean vertical bone resorption of 0.66 mm, compared with 1.25 mm for the NobelSpeedy Groovy implants (P = 0.000); the mean horizontal bone resorption was 0.19 mm for the NobelActive implants and 0.60 mm for the NobelSpeedy Groovy implants (P = 0.000). A high ISQ value was found for both implants, and no statistically significant difference was found for ISQ mean values between interventions (P = 0.941 at baseline; P = 0.454 at implantabutment connection; P = 0.120 at prosthesis delivery). All implants showed good periodontal health at the 3-year-in-function visit, with no significant differences between groups. Conclusion: The results of this research suggest that in well-maintained patients, the MBL changes could be affected by the different implant design. After 4 months of unloaded healing, as well as after 3 years in function, both implants provided good results, however vertical and horizontal bone loss had statistically significant differences between the two groups (difference of 0.58 ± 0.10 mm for the vertical MBL, and 0.4 ± 0.05 mm for the horizontal MBL), with lower values in the Nobel Active implants, compared to the NobelSpeedy Groovy implants. Keywords: bone level, bone loss, dental implants, platform shifting, implant-abutment interface