Previous studies have compared the effectiveness of chemonucleolysis with surgery, but currently, no objective criteria have been correlated with the clinical outcome. The authors reviewed 28 cases where the patients had undergone chymopapain injection to determine the significance of disc herniation size, disc space height reduction, and the duration of symptoms on clinical outcome. All patients had a complete history, physical examination, and discogram, and most had pre- and post-injection computerized tomography (CT) or myelogram. Nine of the 28 patients were considered clinical failures. Seven underwent laminectomy and discectomy and were improved markedly. Two patients were advised to have surgery but refused and were considered clinical failures. The causes of failure were unknown in three patients, free fragment in two patients, and diabetic neuropathy in one. Only two patients who did well showed complete resolution of the disc deformity on repeat CT scan. The remainder still had evidence of an avascular deformity that persisted although reduced in size. The failures showed no changes in disc size. The height of the disc space was too variable to be correlated with clinical outcome. Patients who failed had a longer duration of symptoms than the ones who did well (15.1 months for failure vs. 5 months). Therefore, some reduction of disc deformity size, but not necessarily complete reduction, is necessary for a good result, and the enzyme is not as effective in patients with long-standing symptoms.