Study Design. A systematic review of randomized controlled trials. Objectives. To assess the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors in the treatment of nonspecific low back pain and to assess which type of NSAID is most effective. Summary of Background Data. NSAIDs are the most frequently prescribed medications worldwide and are widely used for patients with low back pain. Selective COX-2 inhibitors are currently available and used for patients with low back pain. Methods. We searched the MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials up to and including June 2007 if reported in English, Dutch, or German. We also screened references given in relevant reviews and identified trials. Randomized trials and double-blind controlled trials of NSAIDs in nonspecific low back pain with or without sciatica were included. Results. In total, 65 trials (total number of patients = 11,237) were included in this review. Twenty-eight trials (42%) were considered high quality. Statistically significant effects were found in favor of NSAIDs compared with placebo, but at the cost of statistically significant more side effects. There is moderate evidence that NSAIDs are not more effective than paracetamol for acute low back pain, but paracetamol had fewer side effects. There is moderate evidence that NSAIDs are not more effective than other drugs for acute low back pain. There is strong evidence that various types of NSAIDs, including COX-2 NSAIDs, are equally effective for acute low back pain. COX-2 NSAIDs had statistically significantly fewer side effects than traditional NSAIDs. Conclusion. The evidence from the 65 trials included in this review suggests that NSAIDs are effective for short-term symptomatic relief in patients with acute and chronic low back pain without sciatica. However, effect sizes are small. Furthermore, there does not seem to be a specific type of NSAID, which is clearly more effective than others. The selective COX-2 inhibitors showed fewer side effects compared with traditional NSAIDs in the randomized controlled trials included in this review. However, recent studies have shown that COX-2 inhibitors are associated with increased cardiovascular risks in specific patient populations.