OBJECTIVES To determine the efficacy and carryover effects of diacerein vs diclofenac in Indian population with knee osteoarthritis (OA). STUDY DESIGN After one week NSAIDâ€™s washout period, patients received either diacerein or diclofenac or combination for 12 weeks with 4 weeks follow-up to determine the carryover effects of the drugs. The primary efficacy end point was the change from baseline in 100mm visual analog scale (VAS) score after 20 meters walk.Â The secondary efficacy end points were the percent change from baseline in pain, stiffness, function and total WOMAC scores. Lequesne impairment index (LII), Knee society score (KSS), and acetaminophen intake. RESULTS Out of 189 patients screened, 81 patients with painful knee OA were randomized and 77 completed the study. At 16 wks, diacerein showed superiority to both diclofenac and the combination therapy as assessed (95% CI) with 100mm VAS score (p<0.05), WOMAC scores (p<0.001), as well as LII, KSS and acetaminophen consumption (p<0.001), demonstrating the carryover effect of the drug. Intra-group comparison showed significant difference in all WOMAC scores from baseline score in each group. Diacerein was safe, well tolerated and caused diarrhea as the frequent adverse effect. CONCLUSIONS Diacerein is safe and effective with long carryover effect.