12 RCTs with a total of 1732 knee osteoarthritis patients were included in this systematic review and meta-analysis comparing diacerein (n=861) to NSAIDs (n=871) for symptom control. The pooled outcomes of interest included the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis index, pain on a Visual Analog Scale (VAS), global efficacy, and the incidence of adverse events. The results of the meta-analysis demonstrated no difference in pooled WOMAC or VAS pain scores; however, 4 weeks post-treatment, pooled WOMAC and VAS pain scores were significantly better in the diacerein group. Global treatment efficacy (as judged by the patients) was significantly in favor of the diacerein group. No difference in the likelihood of adverse events was observed between the two groups. Sub-group analyses by NSAID type revealed no differences between diacerein and celecoxib, diclofenac sodium, or piroxicam in both WOMAC and VAS pain scores. Diacerein did outperform meloxicam in 1 trial with respect to VAS pain scores.