The purpose of the present study was to evaluate the histological and histomorphometric characteristics of post-extraction sites grafted with decellularized bovine compact bone from bovine femur, mixed and unmixed with leukocyte- and platelet-rich fibrin after four months of healing. This study was designed as a randomized controlled trial of parallel groups. Patients in need of a single, implant-supported restoration to replace a hopeless tooth were recruited for tooth extraction and implant placement four months after socket preservation procedure. After tooth extraction, patients were randomly allocated to receive decellularized bovine compact bone from bovine femur, mixed and unmixed with leukocyte- and platelet-rich fibrin. After four months of healing, tapered implants were inserted with an insertion torque between 35 and 45 Ncm. Two months later, implants were loaded with screw-retained definitive crowns. Outcome measures were implant (ISR) and prosthesis (PSR) survival rates, complications, histological and histomorphometric analyses, radiographic marginal bone-level changes, and patients’ satisfaction. Clinical data were collected up to one year after tooth extraction and socket preservation procedures. Thirty patients were consecutively enrolled in the trial (15 in each group). Unfortunately, due to the COVID-19 pandemic, bone samples were collected only in 19 patients. Two implants failed before definitive prosthesis delivery (ISR 93.3%). No prosthesis failed (PSR 100%). Three complications were experienced in the control group. The mean bone percentage was 40.64 ± 18.76 in the test group and 33.40 ± 22.38 in the control group. The difference was not statistically significant (p = 0.4846). The mean soft tissue percentage was 32.55 ± 19.45 in the test group and 55.23 ± 17.64 in the control group. The difference was statistically significant (p = 0.0235). The mean residual graft was 24.59 ± 18.39 in the test group and 11.37 ± 12.12 in the control group. The difference was not statistically significant (p = 0.0992). Mean marginal bone loss, as well as patient satisfaction, showed no differences between groups. With the limitations of the present study, socket preservation with L-PRF mixed with decellularized bovine compact bone demonstrated favorable results, comparing with decellularized bovine compact bone from bovine femur alone. Further studies with larger sample size and longer follow-up are needed to confirm these preliminary results.