ABSTRACT In the United States, adherence for cervical cancer screening decreased from 86% to 77% between 2005 and 2019. Over 50% of cervical cancers are diagnosed in individuals overdue for screening, and promoting access and adherence is essential. Unlike traditional Papanicolaou testing, human papillomavirus (HPV) screening can use self-collected samples, which have comparable sensitivity and specificity to clinician-collected samples. Self-collecting has been shown to increase screening adherence, possibly by circumventing important barriers such as scheduling clinic appointments and negativity about pelvic examinations. Despite this, most individuals in prior studies remained unscreened with low follow-up of HPV-positive results, and kit uptake among populations that are screening adherent or have unknown screening history is unknown. The STEP trial (self-testing options in the era for primary HPV screening for cervical cancer) was a parallel, single-blind, randomized clinical trial comparing cervical cancer screening completion across groups of individuals with due (screening-adherent), overdue, or unknown screening history. Participants were randomized to traditional care (patient reminders and clinician electronic health record [HER] alerts), education (usual care plus educational materials about screening), direct mail (traditional care plus educational materials plus a mailed HPV self-collection kit), or to opt in (traditional care plus educational materials plus the option to request a self-collection kit). Patients were identified using the Kaiser Permanente Washington HER and administrative claims. Eligible participants were females aged 30 to 64 years with current Kaiser Permanente Washington insurance and primary care, intact cervix, who were either due or overdue for screening. The primary study outcome was screening completion within 6 months after randomization, which could be done either in clinic or using the self-collection kit. Modified Poisson regression was used to estimate relative risk (RR) of screening completion for the direct-mail and opt-in groups, relative to the education group. A total of 32,771 participants were randomized between November 2020 and January 2022, of which 13,356 were due for screening, 8682 were overdue, and 10,733 had unknown screening history. Of those due for screening, the RR for screening completion was 1.30 (95% confidence interval [CI], 1.23–1.36; absolute difference, 14.1% [95% CI, 11.2%–16.9%]) for direct mail and 1.07 (95% CI, 1.02–1.12; absolute difference, 3.5% [95% CI, 1.2%–5.7%]) for the opt-in group compared with education. Of those overdue for screening, the RR for screening completion was 1.90 (95% CI, 1.68–2.16; absolute difference 16.9% [95% CI, 13.8%–20.0%]) for direct mail compared with education. Of those with unknown screening history, the RR for screening completion was 1.14 (95% CI, 1.03–1.25; absolute difference 2.2% [95% CI, 0.5%–3.9%]) for the opt-in group compared with education. The results of this randomized controlled trial showed that directly mailing HPV self-collection kits increased cervical cancer screening by over 14% compared with education alone. The effect was similar between participants that were due or overdue for screening, and an opt-in approach was found to minimally increase screening.