Palmoplantar pustulosis (PPP) is a chronic recurring and refractory pustular dermatosis. To investigate the efficacy and safety of arotinoid ethylester in patients with PPP, sixteen adult subjects with PPP, who had taken no systemic medications for three months, were enrolled. All the subjects received 0.03 mg of arotinoid ethylester once daily as initial dosage. The number of pustules and lesion area index (LAI) were measured pre- and post-treatment. Repeated measures of one factor ANOVA was used to statistically analyze the data. After 3 months of treatment, pustules disappeared completely in all patients (F = 15.04; p < .0001); LAI decreased significantly (F = 24.54; p < .0001). Complete clearance (100% reduction of LAI and complete disappear of pustules) and near complete clearance (75%-99%) occurred in 6 and 8 patients, respectively; the other two patients exhibited partial clearance (50%-74%). Side effects were observed in 10 patients, but were mild to moderate and well tolerated. Our study suggested that arotinoid ethylester is an effective therapy for PPP with minimal side effects.