Patients who have high body mass indices can have disabling medial compartment knee osteoarthritis, which might benefit from unicompartmental knee arthroplasty (UKA). The purpose of this study was to compare clinical and radiographic outcomes of UKAs in patients with body mass indices (BMIs) greater and less than 35 kg/m². Thirty-four patients (40 knees) had BMIs of 35 kg/m² or greater, whereas the remaining 33 patients (40 knees) had BMIs below 35 kg/m², with 2-year minimum follow-up. In the high-BMI group, 5 knees were revised to total knee arthroplasty, compared with none in the lower BMI group. Knee Society scores were lower in the surviving high-BMI knees. All surviving components were radiographically stable. The results suggest that UKA should be approached with caution in patients who have high BMIs.