No previous controlled studies have been specifically designed or adequately powered to show the efficacy of topical oxybutynin for palmar hyperhidrosis by using quantitative measures. To evaluate efficacy of 20% oxybutynin hydrochloride lotion (20% OL) in reducing palmar sweat volume in patients with primary palmar hyperhidrosis (PPHH). In a randomized controlled trial, Japanese patients with PPHH aged 12years and older received either 20% OL (n=144) or placebo (n=140) on both palms once daily for 4weeks. Palmar sweat volume was measured by the ventilated capsule method. For the primary outcome, response was defined as a reduction of sweat volume of at least 50% from baseline. At week 4, the responder rate for sweat volume was significantly higher in the 20% OL arm than in the placebo arm (52.8% vs 24.3%, respectively; treatment difference, 28.5% [95% CI, 17.7% to 39.3%]; P<.001). No serious adverse events occurred, and no adverse events led to treatment discontinuation. The treatment period was only 4weeks. In patients with PPHH, 20% OL is superior to placebo in reducing palmar sweat volume.