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Abstract Background: The newest high-risk human papillomavirus (HPV) detection techniques were included for cervical cancer primary screening under the Spanish National Health System in 2019. These analyses allow changing population approaches to foster adherence to screening. Therefore, the validity of self versus conventional sampling for HPV and cytology analyses was appraised. Women's preferences concerning samples and devices were also evaluated. Methods: This is a diagnostic accuracy cross-sectional study among 120 women recruited from a colposcopy clinic at a general hospital in Illes Balears, Spain. Participants were given written information and asked for a self-sample. One of two sets containing two devices each were handed. One set was transported dry and the second in liquid medium. Next, clinicians collected vaginal samples that were our gold standards. The agreement between both techniques was examined with the Kappa coefficient (κ). Next, self-sampling evaluation and preferences for different vaginal devices were surveyed. Results: The agreement between self and conventional samples concerning HPV positivity was very good (κ 0.86 for Mía by XytoTest® and 0.83 for Viba-Brush®) or reasonable (κ 0.73 for Iune and 0.68 for viscose swab). Pap smears from self-samples exhibited moderate agreement (κ 0.41 for Mía® and 0.51 for Viba-Brush® respectively) for negative versus ASC-US and worse results. Most of the participants considered self-sampling as beneficial (110 or 91.7%) and the advantages were, in decreasing order, scheduling, comfort, privacy and less fear for pain or disturbance. The priority of choice for the devices was Mía® and viscose swab (chosen in first or second place) in opposition to Viba-Brush® and Iune (chosen in third or fourth place). If Viba-Brush® was to collect the best quality samples, 108 women (94.7%) switched their decisions. Conclusions: Our agreement between self and conventional samples was very good or reasonable for HPV, with the best values for devices in a liquid medium, and moderate for cytology. Even so, reflex cytology on self-samples is a valuable tool in promoting adherence. Self-sampling was widely accepted for smooth and thin devices. However, there is no resistance to change to others if a higher quality of the sample is obtained.