BACKGROUND: Morton's interdigital neuroma, caused by compression of the interdigital nerve, often requires surgery when conservative treatment fail. This study compared open neurectomy and percutaneous intermetatarsal ligament release (PILR), focusing on various predictive factors. METHODS: A retrospective study, comprising 46 patients (58 feet) with Morton's neuroma who underwent either open excision (n = 24) or PILR (n = 22) from 2012 to 2022. Data included demographics, MRI-measured neuroma size, complications, and revision surgery. Outcomes were assessed using the Visual Analog Scale (VAS), Foot and Ankle Ability Measure (FAAM), and satisfaction scores. RESULTS: Open excision yielded better outcomes than PILR for neuromas larger than 7.40 mm, with lower VAS scores (2.3 vs. 3.9), higher FAAM scores (87 vs. 72), and greater satisfaction (3.2 vs. 2.1). Neuroma width predicted outcomes in the PILR group. CONCLUSION: Open excision is superior for larger neuromas, while PILR may suit smaller ones (<
7.40 mm). LEVEL OF EVIDENCE: Level III cohort study CLINICAL RELEVANCE: This study highlights the importance of neuroma width in determining the success of percutaneous intermetatarsal ligament release (PILR). Our findings suggest that PILR may be more appropriate for smaller neuromas (<
7.40 mm), while open excision offers better outcomes for larger neuromas. This insight could guide surgeons in selecting the most suitable surgical approach, optimizing patient outcomes, and minimizing complications.