Objective: To compare the depth of necrosis achieved using CO2- and N2O-cryotherapy. Method: We treated 20 women with CO2-cryotherapy and 20 with N2O-cryotherapy 24 h prior to undergoing total hysterectomy for reasons unrelated to cervical cancer. Depth of necrosis in the ectocervix was measured on surgically removed tissue. Results: The mean depth of necrosis for the anterior lip achieved by N2O-cryotherapy was 5.3 mm compared with 3.4 mm by CO2-cryotherapy (P < 0.001). We found similar results for the posterior lip (5.0 vs 3.1 mm; P < 0.001). N2O-cryotherapy was more likely than CO2-cryotherapy to achieve a depth of necrosis of ≥ 4.8 mm for the anterior lip (75% vs 15%; P < 0.001) and posterior lip (60% vs 5%; P < 0.001). Conclusions: Our study showed that CO2-cryotherapy may not achieve the depth of necrosis necessary to completely destroy cervical precancer and therefore may be less robust than N2O-cryotherapy. © 2007 International Federation of Gynecology and Obstetrics.