In recent experimental studies, we could demonstrate the occurrence of antibodies against the prosthesis matrix and coating following implantation of polyester-based vascular grafts. Therefore, this study aimed at evaluating the biocompatibility of a new absorbable polymer coating by detection of antibodies against the coating and the polyester matrix. Two polyester vascular prostheses coated either with the polymer (PP-prosthesis) or with gelatine (PG-prosthesis) were functionally implanted into sheep (n = 22 per group). Blood was drawn on days 1 (pre-OP) and 7, 14, 28, 56, 84, 140 (post-OP). Homogenates from both prostheses (PP-target or PG-target) or from an uncoated prosthesis (P-target) were used as assay targets in a particle-based immunoassay. The antibody binding against the P-target was significantly higher in the PP-group than in the PG-group on days 7-56, but not on days 84 and 140. Within both groups, no significant differences but a significant correlation between the binding against the P-target and the coated target was found. Therefore, the absorbable polymer did not induce a specific humoral immune response. In conclusion, the overall immunogenicity of the polymer-coated graft was comparable to the gelatine-coated graft. The detection of prosthesis-specific antibodies seems to be useful for in vivo biocompatibility testing.