Of 410 patients with refractory herniated lumbar disc disease treated with intradiscal collagenase, 82 (20%) did not respond to enzyme treatment and subsequently underwent surgery. Failure to improve in 6 to 8 weeks was the predominant cause for surgical intervention (53 patients). Increased pain (18 patients), progressing neurological deficit (10 patients), and disc-space infection (one patient) were the other indications for surgery. At surgery, extrusions and/or sequestrations were found in 46 patients, undigested protrusions in 16 patients, and other causes of treatment failure in 14 patients. Six patients had normal findings. There was no evidence of adverse enzyme activity on the surrounding structures. Surgical results showed an overall success rate of 87%, and did not appear to be compromised by the previous enzyme therapy.