Background: In France, approximately 40% of women, including menopausal women, do not participate in cervical cancer screening. Many studies and meta-analyses have shown that self-sampling devices for high-risk human papillomavirus (HR-HPV) testing are valuable tools to increase participation. The success of self-sampling screening strategies depends on several factors, including the manner and circumstances in which the women are invited to participate. The acceptability and effectiveness of these strategies should be evaluated before further implementation. Objectives: The primary objective is to evaluate the uptake of cervical cancer screening in under-screened women, based on a direct offer of a vaginal self-sampling device by a midwife. Design: RIDECA is an interventional research project located in the South of France. Methods and Analysis: Six hundred women aged 50–65 with no cervical smear or HR-HPV test for 3 years or more will be recruited at two sites. The device will be offered to enrolled women to utilize at home and return to the Montpellier Hospital laboratory for HR-HPV testing. Completion of self-sampling by women who have accepted the device and follow-up of those with positive HR-HPV DNA tests will be monitored. During recruitment, participants will complete questionnaires on their socio-economic environment and motivational factors based on the psychosocial I-Change model. Semi-structured interviews will be conducted with a sub-group to identify barriers and levers to participation. Statistical analyses will be conducted for the full research sample and for each recruitment site. Ethics: The project was approved by the Ethical Research Committee Ile de France VI and by the French Data Protection Authority. Discussion: The results will provide useful information on the effectiveness (acceptability, efficiency) of this outreach strategy and identify barriers and levers that facilitate its implementation. Registration: ClinicalTrials.gov (NCT04716127), January 20, 2021.