The aim of this study was to evaluate the effect of implant surface treatment with carboxyethylphosphonic acid and fibroblast growth factor 2 on the bone-implant interface during the osseointegration period in vivo using an animal model. The present research was carried out in six minipigs, in whose left tibia implants were inserted as follows: eight implants with a standard surface treatment, for the control group, and eight implants with a surface treatment of carboxyethylphosphonic acid and immobilization of FGF-2, for the test group. At 4 weeks after the insertion of the implants, the animals were sacrificed for the histomorphometric analysis of the samples. The means of the results for the implant-bone contact variable (BIC) were 46.39 ± 17.49% for the test group and 34.00 ± 9.92% for the control group; the difference was not statistically significant. For the corrected implant-bone contact variable (BICc), the mean value of the test group was 60.48 ± 18.11%, and that for the control group, 43.08 ± 10.77%; the difference was statistically significant (-value = 0.035). The new bone formation (BV/TV) showed average results of 27.28 ± 3.88% for the test group and 26.63 ± 7.90% for the control group, meaning that the differences were not statistically significant (-value = 0.839). Regarding the bone density at the interthread level (BAI/TA), the mean value of the test group was 32.27 ± 6.70%, and that of the control group was 32.91 ± 7.76%, with a -value of 0.863, while for the peri-implant density (BAP/TA), the mean value of the test group was 44.96 ± 7.55%, and that for the control group was 44.80 ± 8.68%, without a significant difference between the groups. The current research only found a significant difference for the bone-implant contact at the cortical level; therefore, it could be considered that FGF-2 acts on the mineralization of bone tissue. The application of carboxyethylphosphonic acid on the surface of implants can be considered a promising alternative as a biomimetic coating for the immobilization of FGF-2. Despite no differences in the new bone formation around the implants or in the interthread or peri-implant bone density being detected, the biofunctionalization of the implant surface with FGF-2 accelerates the mineralization of the bone-implant interface at the cortical level, thereby reducing the osseointegration period.