Although bone morphogenetic protein-2 (BMP-2) is widely used for spinal fusion, some concerns cannot be ignored. The combination of growth factor with composite scaffolds represent a promising approach to promote bone regeneration and spinal fusion. Recent studies have demonstrated that the growth differentiation factor-5 (GDF-5) variant BB-1, combining the osteogenic activity of BMP-2 with the angiogenic features of GDF-5, enhanced bone regeneration during long-bone healing in lower-order animals. The study aimed to investigate the efficacy and safety of BB-1 loading on composite scaffolds on spinal fusion in nonhuman primates. Six healthy rhesus monkeys were used to establish a clinically relevant two-segment spinal fusion model. Blank scaffolds or BB-1-loaded scaffolds were implanted into each animal and distributed in a blinded way. Imageological and histological examinations as well as bone histomorphometry were performed after euthanization at 6 months post-operation. BB-1 led to a higher spinal fusion rate (5/6) compared to the negative control (1/6). Mechanically, BB-1 stimulated bone formation and vessel formation. Furthermore, we found that BB-1 increased the density of H-type vessels in the newly formed bone tissues for the first time. Moreover, 500 ​μg BB-1 triggered no local inflammation response in each spine segment and no systematic toxicity in liver and kidney. These results suggest that BB-1 promotes spinal fusion in rhesus monkeys by coupling of angiogenesis and osteogenesis and that local usage of 500 ​μg BB-1 should be effective and safe, facilitating translation of BB-1 from bench to bedside.