This is a prospective, randomized, controlled trial that compared the efficacy of different protocols of local tissue infiltration with levobupivacaine or levobupivacaine-methylprednisolone at the surgical site for pain relief after lumbar discectomy. The objective of the study was to determine the efficacy of preemptive wound infiltration with levobupivacaine and levobupivacaine-methylprednisolone at the surgical site for pain relief. Patients usually suffer significant pain after lumbar discectomy. Wound infiltration with local anesthetics with or without corticosteroids is one method to address this. A total of 100 patients were randomly allocated to five equal groups as follows: Group I had the musculus multifidi near the operated level infiltrated with 30 mL 0.25% levobupivacaine and 40 mg methylprednisolone just before wound closure; Group II had the same region infiltrated with 30 mL 0.25% levobupivacaine alone before closure; Group III had this region infiltrated with 30 mL 0.25% levobupivacaine and 40 mg methylprednisolone before the incision was made; in Group IV this region was infiltrated with 30 mL 0.25% levobupivacaine alone before incision; and in Group C (controls) this region was infiltrated with 30 mL 0.9% NaCl just before wound closure. Demographics, vital signs, postoperative pain scores and morphine usage were recorded. All four treatment groups showed significantly better results than the control group for most parameters. The treated groups had lower parenteral opioid requirements after surgery, lower incidences of nausea and shorter hospital stays. Further, the data indicate that, compared with infiltration of these drugs at wound closure, preemptive injection of levobupivacaine or levobupivacaine-methylprednisolone into the muscle near the operative site provides more effective analgesia after lumbar discectomy. Our data suggest that preemptive infiltration of the wound site with levobupivacaine alone or combined with methylprednisolone provides effective pain control with reduced opiate dose after unilateral lumbar discectomy.