The aim of this open clinical trial was to evaluate the therapeutic effectiveness of CO2 laser vs. loop electrosurgical excision/fulguration procedure (LEEP) in 28 patients with vulvar intraepithelial neoplasia (VIN) (mean linear extent = 6 cm2). To avoid selection bias, in each patient half of the lesional area was treated with CO2 laser excision/vaporization and the other half was electro-excised/fulgurated. All but three patients (89%) were followed for a minimum of 9 months, maximum 26 months, mean 12 months after last therapy. Complete response was obtained in 12 of 25 patients (48%) after a single laser/LEEP most of whom had 6 cm2 or less lesional area. Repeated treatments(mean 3) yielded 19 of 25 (76%) disease-free patients at 9 months or longer. There was no significant (χ2) difference between the CO2 laser- or LEEP-treated areas with respect to recurrence of disease, healing time (mean 18 days), postoperative discomfort (61%) and complications (11%)). The overall operating time when controlled for lesional size was twice as fast with the CO2 laser (mean 8 min) than LEEP (mean 20 min). Laser and LEEP were more suitable for ablational and excisional procedures, respectively. LEEP may be an alternative to CO2 laser for treating VIN, particularly those with a linear extent less than 6 cm2.