ABSTRACT: Primary hyperidrosis (PH) is a disorder characterized by excessive eccrine sweat gland production that primarily involves the axillae as well as palms and soles. Common first-line topical treatment for PH consists of aluminum salts (AS) that act by physically blocking eccrine sweat gland ducts. However, primary irritant contact dermatitis is a common side effect of AS treatment. Recently, a new low-residue, thermophobic foam formulation containing 20% aluminum sesquichlorhydrate has been developed (Nidrox®, Mipharm S.p.A.). To evaluate the local tolerability and efficacy of 20% aluminum sesquichlorhydrate foam in the treatment of axillary and palmar PH. Twenty subjects affected by PH were enrolled in a multicenter, open-label study. Local tolerability was evaluated by physicians assessing itching, burning, and skin irritation using a four-point score (from 0: no symptoms to 3: severe symptoms). Skin irritation was quantified with a visual score. Efficacy was assessed by means of Minor test score using a four-point score (range 0–3). The foam was applied to clean dry skin, every night during the first 2 weeks and three times a week during the following 2 weeks. Clinical evaluations were performed at baseline, at day 14 and at day 28. Patients were monitored throughout the study for adverse events. All 20 subjects completed the study. The foam induced a significant reduction of the Minor score in comparison with baseline values (p = 0.0002) both at day 14 and at day 28. At the end of the 4-week treatment period, the foam reduced eccrine sweating by 61% (Minor score: 3.3 vs. 8.5). No skin irritation was observed during the trial except for one subject who experienced a mild and transient itching sensation. No other side effects were reported during the study. This new foam appears to be an effective and well-tolerated topical treatment in reducing sweating in patients with axillary and palmar PH.