Background context The use of nonsteroidal anti-inflammatory drugs (NSAIDs) had been implicated as a risk factor for nonunion in spinal fusion. Even with a number of animal and human studies suggesting NSAIDs either delay or inhibit spinal fusion rates, these drugs continue to be used because of demonstrated benefits. Diclofenac sodium is no exception. It is very popular as a first-line treatment for acute pain, even perioperatively for spine fusion patients. Review of published literature reveals no studies done on the effect of diclofenac sodium on spine fusion rates. Purpose To determine if diclofenac sodium is a risk factor for delayed union and nonunion in adult patients who underwent one- to two-level instrumented posterior lumbar interbody fusion (PLIF) using only local autogenous bone graft. Study design/setting Retrospective, analytical. Patient sample Two hundred and seventy-three adult patients who underwent one- to two-level PLIF with minimum 2-year follow-up. Outcome measures Diclofenac sodium intake, fusion status. Methods Medical records and radiographs of 273 adult patients who underwent one- to two-level PLIF in a single institution from 1999 to 2004 were reviewed. All patients did not use any NSAID or steroid perioperatively, except for diclofenac sodium postoperatively. The amount of diclofenac sodium used was quantified for the first 14 days post-op. These patients were followed-up periodically for 2 years. Demographic data, levels fused, and NSAID intake were correlated to union status. Results Nineteen out of the 273 patients had no diclofenac sodium intake (no-dose group), 168 patients used less than or equal to 300 mg (moderate-dose group), and 86 patients used more than 300 mg of diclofenac sodium (high-dose group). There were 4 nonunions and 41 delayed unions seen. No significant difference was seen when fusion status was compared with age, sex, L5–S1 versus other levels, and smoking history (all comparisons, p>.05). There was a significant difference between one- and two-level fusions in terms of union status (p=.002). There were no nonunions and 18 delayed unions seen in 217 patients in the single-level fusion group. All 4 nonunions and 23 delayed unions were noted among the 56 patients in the two-level group. There were no cases of delayed union and nonunion in the no-dose group. There were also no nonunions but 16 delayed unions in the moderate-dose group. There were 4 nonunions and 25 delayed unions in the high-dose group. As diclofenac sodium intake increases, the incidence of delayed union and nonunion were also seen to increase (p<.001). Time to union was correlated to the amount of diclofenac sodium intake using Pearson's correlation coefficient (r=0.271, p<.001). When the patients were divided into one- and two-level fusion groups, the amount of diclofenac sodium used still had a significant positive correlation to frequency of delayed union and nonunion and in time to union in each group (all comparisons, p<.05). Conclusions Diclofenac sodium showed a dose-dependent inhibitory effect toward spine fusion especially when used during the immediate postoperative period. No significant correlation was seen between age, sex, L5–S1 versus other levels fused and smoking history when compared with spine nonunion. Two-level lumbar fusions also showed a significant negative correlation to spine fusion compared with single-level fusions.