Purpose: This in vivo study used control variable implants to compare early bone responses in fluoride-modified (F-mod) and hydrophilic, sandblasted, large-grit, acid-etched (modSLA) surface implants that differed in implant design. Materials and Methods: Four different types of implants (n = 24) were prepared: F-mod surface with Astra Tech implant design; modSLA surface with Straumann implant design; sandblasted, large-grit, acid-etched (SLA) surface with Astra Tech design; and SLA surface with Straumann implant design. Scanning electron microscopy, confocal laser scanning microscopy, and x-ray photoelectron spectroscopy were performed to assess implant surface characteristics. Four implants from each implant type were inserted in the tibiae of four rabbits that were sacrificed 10 days after surgery. Bone-to-implant contact (BIC) and bone area (BA) were measured to evaluate early bone responses. Analysis of variance with Tukey's multiple comparison method was used for the histomorphometric data to find any significant difference. The surface characteristic-related data were analyzed using the Kruskal-Wallis test. The level of significance was .05 in statistical analyses. Results: No significant differences in BIC and BA were found among the modified surfaces (P > .05), whereas significant differences were found in surface topography and surface chemistry. The different designs showed no significant effects on early bone responses when identical surface modifications were applied (P > .05). Conclusion: F-mod and modSLA surfaces showed no significant differences in early bone responses. Furthermore, the implant design had no influence on the bone response. This in vivo experimental model will help improve the evaluation of surface modification factors by allowing an independent estimation of one variable (surface modification) against a constant (implant design). Keywords: control variable, fluoride-modified, hydrophilic SLA, implant design, SLA