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The influence of ketorolac on spinal fusion was studied in a retrospective review of 288 patients who underwent an instrumented spinal fusion.To assess the effect of postoperative ketorolac administration on subsequent fusion rates.Nonsteroidal anti-inflammatory drugs are widely used compounds, which are known to inhibit osteogenic activity and have been shown to decrease spinal fusion in an animal model. No previous studies have examined the influence of nonsteroidal anti-inflammatory drugs on spinal fusion in clinical practice.The medical records of 288 patients who underwent instrumented spinal fusion from L4 to the sacrum between 1991 and 1993 were reviewed retrospectively. The 121 patients who received no nonsteroidal anti-inflammatory drugs were compared with the 167 patients who received ketorolac after surgery. The groups were demographically equivalent.Ketorolac had a significant adverse effect on fusion, with five nonunions in the nondrug group and 29 nonunions in the ketorolac group (P > 0.001). Ketorolac administration also significantly decreased the fusion rate for subgroups including men, women, smokers, and nonsmokers. The odds ratio demonstrated that nonunion was approximately five times more likely after ketorolac administration. Cigarette smoking also decreased the fusion rate (P > 0.01); smokers were 2.8 times more likely to develop nonunion.These data suggest that nonsteroidal anti-inflammatory drugs significantly inhibit spinal fusion at doses typically used for postoperative pain control. The authors recommend that these drugs be avoided in the early postoperative period.