BACKGROUND Diacerein is a drug used in osteoarthritis (OA) that elicits an inhibitory effect on interleukin-1 and metalloproteases. Although diacerein has shown modest efficacy and safety in the treatment of knee and hip OA, there have been no placebo-controlled clinical trials for hand OA. OBJECTIVE The aim of the current study was to investigate the efficacy and tolerability of diacerein in patients with hand OA. METHODS Patients fulfilling the American College of Rheumatology criteria for hand OA participated in this randomized, double-blind, placebo-controlled study. Eligible patients were >40 years of age, had at least 1 tender joint, and had a joint pain visual analog scale of >30 mm. Patients received diacerein (50 mg) or placebo BID for 12 weeks. The primary end point was the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score at 4 weeks. Secondary end points were AUSCAN pain score at 12 weeks and AUSCAN physical function and stiffness score, patient and physician global assessment, functional index of hand OA scores, and multidimensional health assessment questionnaire results at 4 weeks and 12 weeks. RESULTS Eighty-six Korean patients were enrolled (42 diacerein, 44 placebo). The intention-to-treat and per-protocol analyses revealed no significant differences between the 2 groups in terms of change in AUSCAN pain score at 4 weeks, except for improvement in physician global assessment at 4 weeks (per-protocol analysis, P = 0.004). The safety profile of diacerein was comparable to placebo, except for frequent discoloration of the urine (88% vs 20%). CONCLUSIONS These results suggest that diacerein 50 mg BID may be ineffective in controlling the symptoms of hand OA. ClinicalTrials.gov identifier: NCT00685542.