Objective: Our study aimed to analyze imatinib’s efficacy, tolerability, and safety in treating naive patients with unresectable and progressive desmoid tumors. Material and Methods: The data of patients who were ≥18 years old diagnosed with desmoid tumors treated with imatinib were evaluated retrospectively regarding their demographic features, comorbidities, disease stage, pathological features of the tumor, and response rates and progression-free survival (PFS). Results: In our study, 36 patients with advanced desmoid tumors receiving imatinib with a median age of 28 [interquartile range (IQR): 21-40] of whom 58.3% were female were included. The patient’s complete response, partial response, stable disease, and progressive disease with imatinib 800 mg/day were 13.9%, 44.4%, 27.7%, and 13.9%, respectively. The Grade-3 adverse events, including neutropenia (n=3, 8.3%) and rash (n=3, 8.3%), were relieved after dose reduction. The median PFS was 29 months (95% confidence interval, 16-42 months) with imatinib, and only 3 (8.3%) patients were exitus due to disease progression during the follow-up (median: 43 months, IQR: 24.3-70.8). Conclusion: Our study provided clinical evidence of the efficacy and safety of imatinib in patients with desmoid tumors with real-world experience. However, appropriately designed randomized-controlled clinical trials are needed to explore the effectiveness of imatinib in desmoid tumors to provide an alternative management approach.