Cooling of thermosensitive patients with multiple sclerosis (MS) can improve clinical symptoms. In order to study the effectiveness of an advanced lightweight cooling-garment technology based on aquatic evaporation, a single-blinded balanced crossover study was performed on 20 patients with an Expanded Disability Status Scale score < or =6.5. The results using a tight-cuff cooling-garment prototype for peripheral cooling suggest improvement of a timed-walking test, leg-strength, fine-motor skills and subjective benefits. Preliminary data of the heart rate variability (HRV) including six patients suggest that the MS patients show an abnormal HRV after sham condition, which is normalized after cooling. Technical information was gained about the cooling activity and the practicability and handling of the device. These encouraging findings promote further adaptations of the prototype to increase its cooling properties and ameliorate the practicability of the cooling garment.