OBJECTIVE: To evaluate the interbody fusion efficacy and biocompatibility of a graft-free cage made of polyetheretherketone/calcium silicate composite/porous tantalum (PEEK/CS/pTa cage) compared with a PEEK/CS cage with an autogenous bone graft in a goat model. METHODS: PEEK/CS/pTa and PEEK/CS cages were prepared through an injection-moulding method. The PEEK/CS composites and porous tantalum were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS) mapping. Then, adult goats were chosen for C2/C3 and C3/C4 discectomy via the anterior cervical approach and randomly implanted with PEEK/CS/pTa and PEEK/CS/cages with autogenous bone grafts. The fusion performance and osseointegration of the cages were evaluated by X-ray imaging, magnetic resonance imaging (MRI) scanning, and bone histomorphometry analysis. Moreover, the concentrations of Ca and Si in urine, serum, tissue around the fusion segments and major organs of the goats were determined by inductively coupled plasma-optical emission spectrometry (ICP-OES). Histological observation of major organs of the goats was used to evaluate the biosafety of PEEK/CS/pTa and PEEK/CS cages. RESULTS: X-ray and MRI imaging suggested that both PEEK/CS/pTa cages and PEEK/CS cages maintained similar average intervertebral space heights. The tissue volumes in the fusion area were comparable between the two groups of cages at 26 weeks after surgery. Histological morphometric data showed that PEEK/CS/pTa cages and PEEK/CS cages with autogenous bone grafts had similar bone contact and osseointegration at 12 and 26 weeks. Element determination of serum, urine, spinal cord, dura matter, bone and organs showed that the CS/PEEK cages did not cause abnormal systemic metabolism or accumulation of calcium and silicon in local tissues and major organs of goats after implantation. No obvious pathological changes were found in the heart, liver, spleen, liver or kidney tissues. CONCLUSION: Overall, these results suggested that the graft-free PEEK/CS/pTa cage showed similar bony fusion performance to the PEEK/CS cages with autogenous bone grafts. The cages releasing calcium and silicon had good biological safety in vivo.The translational potential of this article: This study provided a new graft-free interbody fusion solution to patients with degenerative disc diseases, which could avert potential donor-site complications. This study also provided a detailed assessment of element excretion and accumulation of Ca and Si in vivo, which validated the biosafety of this new type of bioactive interbody fusion cage.