Objective To (1) examine the outcome in horses with osteoarthritis or intra-articular soft tissue injuries of the stifle after arthroscopic exploration and debridement and (2) to determine any imaging or surgical findings that may influence prognosis. Design Case series. Animals Horses (n=44) with lameness referable to the stifle, diagnosed with osteoarthritis, meniscal tears, or other intra-articular soft tissue injuries based on arthroscopic examination. Methods Medical records of horses with stifle lameness that had arthroscopic exploration were reviewed. Horses with osteochondrosis lesions, intra-articular fractures, or osseous cyst-like lesions were excluded. Pertinent case information was analyzed and short- and long-term outcome was assessed. Results There was no association between radiographic score and surgery score. Diagnostic ultrasound had a sensitivity of 79% and a specificity of 56% for identifying meniscal injuries. Follow-up information was available for 35 horses; 23 horses (60%) improved after surgery, 16 (46%) became sound, and 13 (37%) returned to their previous level of function. A negative association was observed between age and degree of preoperative lameness and outcome. More severe changes observed on preoperative radiographs were also negatively associated with prognosis. No horses with grade 3 meniscal tears improved postoperatively and increasing meniscal pathology was negatively associated with return to previous function. A weak association between surgery grade and outcome was also observed. Degree of chondral damage, location of primary pathology, and microfracture techniques had no effect on outcome. Conclusions Advanced horse age, severe lameness and preoperative radiographic changes, and presence of large meniscal tears are associated with a negative postoperative outcome for horses with stifle lameness. Appearance of the articular surface at surgery appears to be an inconsistent prognostic indicator. Clinical Relevance Some horses with extensive cartilage damage may return to athletic function after arthroscopic debridement and lavage. A more pessimistic prognosis may be given to older horses, those with more severe preoperative lameness, and those with severe radiographic changes or large meniscal tears.