Objectives To explore the etiology of May-Thurner syndrome (MTS) with acute iliofemoral deep vein thrombosis (DVT) regarding imaging findings and clinical features. Methods We retrospectively analyzed 57 patients with acute left iliofemoral DVT from 2015 to 2020. The diameter of left common iliac vein (LCIV) at the maximal compression site and its percent compression regarding the average diameter of the uncompressed iliac vein were recorded in central and distal portions of the LCIV according to the location in the quadrant of lumbar vertebral body. Compression was categorized into simple and bony MTS; Simple MTS as LCIV compressed by the right common iliac artery (RCIA) versus Bony MTS as LCIV by lower lumbar degenerative changes regardless of RCIA compression. Initial computed tomographic venography (CTV) regarding chronic change of LCIV such as fibrotic atrophy or cordlike obliteration, extent of thrombus, and lumbar degenerative changes were evaluated. Therapeutic effect after initial therapy was assessed in follow-up CTVs after 3–6 months. Results All patients showed LCIV compression with 19 simple MTS (mean age, 42.8 ± 14.1 years [23–67 years]; 12 females; symptom for 4.4 ± 5.5 days) and 38 bony MTS (mean age, 73.0 ± 10.2 years [49–85 years]; 26 females; symptom for 5.5 ± 4.8 days). There was significant difference in age ( p < .001) and no significant difference in sex or symptom duration between two groups ( p = .691 and 0.415, respectively). All simple MTS showed compression only in the central LCIV and half of bony MTS showed compression in both central and distal LCIV ( p < .001). Among the lumbar degenerative changes, symmetric anterolateral osteophyte ( p < .001) and asymmetric osteophyte ( p < .001) were significantly associated with bony MTS, but not scoliosis ( p = .799), compared to simple MTS. Although there was no significant difference in chronic change of LCIV, thrombosis extent, and therapeutic effect between two groups ( p > .05), chronic change of LCIV showed significant difference between single and dual compression (23.7% vs. 57.9%, p = .024) and residual thrombus after initial therapy was occurred in 21.1% of single compression and 47.4% in dual compression with non-significant trend ( p = .082). Conclusion Bony MTS related to lumbar degenerative changes with acute iliofemoral DVT occurs in older patients, presenting more than one stenosis at LCIV, inducing more chronic change with possibly weaker therapeutic effect than simple MTS.