The gold standard treatment in anterior cruciate ligament (ACL) reconstruction involves autologous tissue transplantation, but this can have complications. Artificial grafts are an alternative, but the best option is debated. This study aimed to assess the biocompatibility and integration of a silk fibroin textile prosthesis (SF-TP) with peri-implant bone tissue and the native ACL. Twenty-six sheep underwent ACL reconstruction with SF-TP or autologous femoral fascia lata (FFL). Sheep were divided into two groups (3 and 6 months) and retrieved joints processed for histological, morphometrical and mechanical analysis. In vitro, SF-TP showed no cytotoxicity and good cell interaction up to 14 days. Histology revealed fibro-vascular tissue around SF-TP, with a progressive attempt of ligamentous-like tissue formation at 6 months. However, SF-TP group had higher joint damage scores. Micro-CT showed tunnel enlargement in SF-TP group, while FFL group had a decrease. SF-TP reconstructions had lower stiffness and strength (44 % and 64 % decrease) than those of autologous FFL reconstruction and often failed by pull-out from the bone tunnel due to tunnel enlargement. These results indicate poor osteointegration and graft motion with SF-TP, leading to joint damage/bone resorption and reduced mechanical competence. These results do not support the use of SF-TP for ACL reconstruction.