Most of the metallic devices have to be removed, treating osteochondritis dissecans lesions. This animal study describes the biological and mechanical behavior of screws and pins, made of commercially available PGA/PLA and PLA96 and metallic screws and pins, used for fragment fixation. A sham operation served as control. A tissue reaction with cavity formation was observed around every PGA/PLA screw, beginning at 12 weeks following insertion, in contrast to once around a PLA96 screw (p < 0.001), once around one of the 16 PGA/PLA pins and never around those, made of PLA96 (no significance). Disintegration of the PGA/PLA devices started 6 weeks following implantation against 34 weeks for the PLA96 implants. The gap between the fragment and the recipient cartilage disappeared only in the sham group. Many fragments of PGA/PLA material were found in the synovia, in contrast with just a few fragments in the PLA96 group, causing a mild cellular reaction. No polymer particles were found in the draining lymph nodes at any interval. In conclusion, the tested biodegradable screws should not be used for fragment fixation in the treatment of osteochondritis dissecans. Either an undesirable tissue reaction can be expected (PGAPLA), or, because of the slow degradation (PLLA), a screw might damage the opposite cartilage during weight bearing. Two biodegradable pins provide a safe rotational stability and should be combined with one metallic screw, providing compression. This screw has to be removed before loading the limb to prevent cartilage wear of the opposite tibia plateau.