Silk　was　widely　investigated　as　a　promising　scaffold　material　in　ligament　tissue　engineering.　Although　a　variety　of　silk　scaffolds　were　developed　for　the　regeneration　of　anterior　cruciate　ligament　(ACL)　in　vitro　and　in　vivo,　more　investigations　should　be　performed　in　large　animals　to　translate　these　findings　into　clinical　applications.　The　aim　of　this　study　is　to　evaluate　the　feasibility　of　using　silk-based　ACL　scaffolds　to　regenerate　damaged　ACLs　in　porcine　model.　The　microstructural　organization,　tissue　regeneration　as　well　as　ligament-bone　interface　of　silk　implants　were　evaluated　with　scanning　electron　microscopy,　micro-computerized　tomography,　histological　and　immunohistochemical　staining　at　three　and　six　months　postoperatively.　The　results　demonstrated　that　silk　fibers　in　the　ACL　scaffolds　organized　in　parallel　similar　with　collagen　fibers　in　native　ligaments,　which　facilitated　and　guided　the　penetration　of　newly　regenerated　tissue　into　the　pores　among　silk　fibers.　Collagen　production　especially　collagen　I　in　silk　implants　significantly　increased　from　three　to　six　months,　and　was　gradually　close　to　the　level　of　native　ligaments.　At　implant-bone　interface,　indirect　ligament-bone　insertion　was　observed　at　three　months　and　substantial　Sharpey＇s　fibers　formed　at　six　months.　The　results　indicated　that　the　silk-based　ACL　scaffold　provides　a　promising　tissue　engineering　approach　for　ACL　regeneration.