Failed back syndrome can have any number of causes. For example, the original cause of the pain can recur or there may be complications during surgery. The nerve root causing the pain may be inadequately decompressed, joints or nerves may become irritated during the surgical procedure, or scar tissue may compress or bind nerve roots. In addition, nerve damage, either prior to surgery or during the procedure, will not heal and can contribute to ongoing pain. In some cases, nerves may regenerate to some extent, but even this can cause pain if the regeneration is abnormal. Inadequate or incomplete rehabilitation and physical therapy, especially in patients whose back muscles are deconditioned (out of shape), can cause chronic pain as well.

Spinal fusion surgery, a procedure used to stabilize joints in the spine, usually is very successful, but also carries the risk of failed back syndrome. For this procedure, hooks, rods, and screws are used to fix the spine, and then bone taken from another part of the body or from a bone bank is implanted to encourage bone to grow across the joints. Following surgery, there is a chance that the metal implants will fail, or the bones may fail to fuse for unknown reasons. Also, the fixing of one or more spinal joints may increase the strain on nearby joints. Any of these conditions may lead to ongoing pain.