Aim: To evaluate the medium-term survival and the progression of marginal bone loss by determining the statistical relationship between the explanatory variables for dental implants with internal hexagonal connection in native bone and with guided bone regeneration. Materials and Methods: The present retrospective study was carried out on a total of 218 implants (143 implants in native bone and 75 implants with guided bone regeneration) placed in 53 patients selected without restrictive inclusion criteria. Clinical and radiographic variables, including marginal bone loss, were recorded up to 46 months of follow-up. Mann-Whitney U test was used to compare annual bone loss and total marginal bone loss. The cumulative survival rate was calculated according to the lifetable method and illustrated with Kaplan–Meier survival curves. Univariate and multivariate analysis was performed to investigate the association between study variables and the time to implant failure. Additional factors influencing marginal bone loss were also evaluated. Results: The cumulative survival rates for implants placed in native bone and with guided bone regeneration at 46 months were 97.9% and 97.3%, respectively. In our cohort, the univariate analysis identified marginal bone loss, gingival thickness, and bleeding on probing as risk indicators of implant failure. Moreover, bone loss was correlated with gingival thickness and implant depth. Conclusion: No statistically significant differences in survival rates were reported between two types of implants. On the other hand, the correlation of marginal bone to implant insertion depth and gingival thickness, suggests that the biological width measurement should be respected.