Background: Spontaneous osteonecrosis of the knee has recently been termed subchondral insufficiency fracture of the knee (SIFK) to appropriately recognize the etiology of mechanical overloading of the subchondral bone. The purpose of this study was to assess clinical outcomes of SIFK based on progression to surgical treatment and arthroplasty, and to evaluate the risk factors that increase the progression to arthroplasty. Methods: A retrospective review was performed on patients with a diagnosis of SIFK, as confirmed with use of magnetic resonance images (MRIs). Baseline and final radiographs were reviewed. Baseline MRIs were also reviewed for injury characteristics. Failure was defined as progression to surgical treatment or conversion to arthroplasty. Results: Two hundred twenty-three patients (71% female) with a mean age of 65.1 years were included. SIFK affected 154 femora (69%) and 123 tibiae (55%), with medial compartment involvement in 198 knees (89%); 74% of medial menisci had root or radial tears, with a mean extrusion of 3.6 mm. Varus malalignment was identified in 54 (69%) of 78 knees. Seventy-six (34%) of all patients progressed to surgical intervention at 2.7 years, and 66 (30%) underwent arthroplasty at 3.0 years. The rates of conversion to surgical intervention and arthroplasty increased to 47% (37 of 79; p = 0.04) and 37% (29 of 79; p = 0.09), respectively, in patients with >5 years of follow-up. The 10-year survival rate free of arthroplasty for patients with SIFK on the medial femoral condyle (p < 0.01), SIFK on the medial tibial plateau (p < 0.01), medial meniscal extrusion (p = 0.01), varus alignment (p = 0.02), and older age (per year older; p = 0.003) was significantly higher than the survival rates of those without each respective condition. Conclusions: Subchondral insufficiency fractures predominantly involve the medial compartment of the knee and commonly present with medial meniscal root and radial tears. Approximately one-third of patients progressed to total knee arthroplasty. Baseline arthritis, older age, location of the insufficiency fracture on both the medial femoral condyle and medial tibial plateau, meniscal extrusion, and varus malalignment were all associated with progression to arthroplasty. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.