Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.