We assessed the benefit of bone morphogenic protein-2 (BMP-2) and low-level laser irradiation (LLLI) on the osseointegration of synthetic bone grafts. Synthetic bone grafts are safe alternatives to autografts. BMP-2 and LLLI have been shown separately to improve bone healing. However, their effects have not been evaluated together with synthetic materials. Here, we used a rat model to compare the efficacy of BMP-2 and LLLI on synthetic graft healing. Male Sprague-Dawley rats (n = 35) were divided equally into groups: control (defect only), graft only, graft and BMP-2, graft and LLLI, and a combination of graft, LLLI, and BMP-2. A 3 x 3 mm monocortical tibial defect was filled using a synthetic graft with or without 2 mg/mL BMP-2 pre-treatment. LLLI was performed using an optical fibre and an indium-gallium-arsenide-phosphate laser for 60 s daily for 7 days, delivering 6.0 J/day. Histopathology was performed 4 weeks post-graft using a standardised scoring system (1-5, based on the degree of healing observed). Groups were compared using the MannWhitney U test, with p values < 0.05 considered significant. Osteogenesis was poor in both the control and graft-only groups (1.4 +/- 0.5 and 2.3 +/- 0.5, respectively). BMP-2-(4.3 +/- 0.5), LLLI-(3.7 +/- 0.5), and BMP-2/LLLI-treated (4.7 +/- 0.5) grafts all displayed significantly more healing than the control or graft alone groups (P < 0.001). Both BMP-2 and LLLI significantly improved the osseointegration of synthetic bone grafts. However, no synergy was noted between the therapies.