This study aims to evaluate and compare the Cervex-Brush® and Orcellex® Brush as sampling devices for vaginal vault smear cytology in cervical cancer patients treated primarily with radiotherapy. A randomized crossover trial was conducted at a gynecological oncology center in Hong Kong to compare the Cervex-Brush® and Orcellex® Brush in terms of their vault smear adequacy rate in cervical cancer patients who underwent radiotherapy. One hundred sixty cervical cancer patients treated with primary radiotherapy and undergoing follow-up surveillance by vaginal vault cytology were recruited. The smear adequacy rate was 90.6% for Cervex-Brush® and 91.9% for Orcellex® Brush. The rates of low cellularity for both brushes were similar (76.8% for Cervex-Brush® vs. 76.1% for Orcellex® Brush). The detection rates of abnormal smears were also not significantly different (2.8% for Cervex-Brush® vs. 4.2% for Orcellex® Brush). The 2 brushes were also not significantly different in terms of pain score and degree of bleeding. It was further observed that the second smear collection was more painful and patients who were on hormonal replacement therapy demonstrated less bleeding. There was no difference between the Orcellex® brush and the Cervex-Brush® in terms of smear adequacy rate, rate of high cellularity and the detection of abnormal smears. There was also no significant difference between the 2 brushes in terms of pain and the degree of bleeding. Therefore, the Orcellex® Brush can be considered a suitable alternative sampling device for vault smear collection in patients who have undergone radiotherapy for cervical cancer. ClinicalTrials.gov Identifier: NCT04461574.