The objective of this study was to evaluate an injectable, in situ crosslinkable elastin-like polypeptide (ELP) gel for application to cartilage matrix repair in critically sized defects in goat knees. One cylindrical, osteochondral defect in each of seven animals was filled with an aqueous solution of ELP and a biocompatible, chemical crosslinker, while the contralateral defect remained unfilled and served as an internal control. Joints were sacrificed at 3 (n = 3) or 6 (n = 4) months for MRI, histological, and gross evaluation of features of biomaterial performance, including integration, cellular infiltration, surrounding matrix quality, and new matrix in the defect. At 3 months, ELP-filled defects scored significantly higher for integration by histological and gross grading compared to unfilled defects. ELP did not impede cell infiltration but appeared to be partly degraded. At 6 months, new matrix in unfilled defects outpaced that in ELP-filled defects and scored significantly better for MRI evidence of adverse changes, as well as integration and proteoglycan-containing matrix via gross and histological grading. The ELP-crosslinker solution was easily delivered and formed stable, well-integrated gels that supported cell infiltration and matrix synthesis; however, rapid degradation suggests that ELP formulation modifications should be optimized for longer-term benefits in cartilage repair applications.