Background: No consensus has been reached in the treatment of Frieberg disease. Our aim was to evaluate medium- to long-term results of patients with advanced Freiberg disease managed with extensor digitorum brevis tendon interpositional arthroplasty. Methods: There were 24 patients (19 females, 5 males) managed with interpositional arthroplasty for advanced Freiberg disease between 2003 and 2015. The mean follow-up was 133.8 (range, 60-198) months. According to Smillie classification, there were 4 grade 3, 13 grade 4, and 7 grade 5 patients. Patients were evaluated preoperatively and at the final follow-up with the American Orthopaedic Foot & Ankle Society (AOFAS) score and metatarsophalangeal joint range of motion and postoperatively with visual analog scale (VAS) and subjective satisfaction evaluation. Joint space was evaluated on x-rays. Results: Mean AOFAS score increased (53.9 to 80.3, P = .001). Eight patients had excellent, 14 had good, and 2 had fair scores. A significant increase was found in dorsiflexion (38.1° [24°-52°] vs 55.3° [34°-65°]; P = .001) and plantarflexion (19.0° [10°-28°] vs 28.6° [19°-39°]; P = .001). Narrowing of the joint space was not seen in any patient, but expansion was determined in all patients (0.39 [0.35-0.47] vs 0.44 [0.41-0.47] cm; P = .002). Of the patients, 9 were very satisfied, 12 were satisfied, 2 were moderately satisfied, and 1 was dissatisfied. The mean postoperative VAS pain score was 1.7 ± 0.9 (0-4). Conclusion: After a minimum 5-year follow-up, most patients with Freiberg disease managed with interpositional arthroplasty using the extensor digitorum brevis tendon had excellent to good functional results with a widening of the joint space. Level of Evidence: Level IV, retrospective case series.