The aims of this randomized controlled trial were to evaluate the efficacy of intra-articular Hylan G-F 20 on the pain, pinch strength, and functional status in patients with thumb base osteoarthritis (OA). Sixty-six hands of 33 female patients (mean age, 62.6 +/- 6.4 years) with bilateral clinical and radiological thumb base OA were included into this study. Hands of the same patient were divided to Hylan G-F 20 and saline-injection groups. VAS pain 100 mm, pinch strength (key, tripod and pulp to pulp pinch) and functionality (Dreiser functional index) were assessed at baseline, at sixth and 24th weeks. Statistically significant improvements were detected in function (p = 0.001), VAS pain (p = 0.002), and pinch strength (p = 0.004) at the 24th week in the Hylan G-F 20 group. However, only VAS pain scores decreased temporarily in control hands at the 6th week (p = 0.02). Although short-term placebo analgesic effect could not be ignored, intra-articular hylan was effective on pain, pinch strength, and function at the 24th week.