Surgery is often the treatment of choice for lumbar disc herniation (LDH) with severe leg pain. This study aimed to investigate the efficacy of Condoliase chemonucleolysis (CC) in patients who were nonambulatory because of severe leg pain. A total of 58 patients who underwent CC for conservative treatment-resistant LDH were included in this study. Changes in the leg and lower back pain evaluated using the numeric rating scale (NRS) were retrospectively assessed at three time points (1 week, 1 month, and 3 months after treatment). Patients were divided into the ambulatory group (group A) and nonambulatory group (group N) based on their ambulatory status. The clinical and radiological findings including magnetic resonance images were compared between the two groups. Of the 58 patients, 16 (28%) who could not walk independently because of severe leg pain were included in group N. Group N showed significantly higher mean NRS score for leg pain (NRS-LP) before treatment than group A (group N, 7.9; group A, 6.8; p = 0.009). Changes in the mean NRS-LP from pretreatment to 1 week were significantly higher in group N (group N, 5.2; group A, 3.4; p = 0.02). In group N, the mean NRS-LP decreased significantly over time, and 69% of the patients were ambulatory after 1 week, 88% after 1 month, and 94% after 3 months. CC provides early pain relief and can be an immediate treatment option for patients who cannot walk independently because of severe leg pain.