ObjectivesThe incidence of cervical cancer is up to 20-fold higher among First Nations women in Canada than the general population, probably due to lower participation in screening. Offering human papillomavirus (HPV) self-sampling in place of Papanicolaou (Pap) testing may eventually increase screening participation and reduce cervical cancer rates in this population.DesignA community-randomised controlled screening trial.SettingFirst Nations communities in Northwest Ontario, Canada.ParticipantsWomen aged between 25 and 69, living in Robinson Superior Treaty First Nations. The community was the unit of randomisation.InterventionsWomen were asked to complete a questionnaire and have screening by HPV self-sampling (arm A) or Pap testing (arm B).Primary outcome measuresThe number of women who participated in cervical screening.RandomisationCommunity clusters were randomised to include approximately equivalent numbers of women in each arm.Results6 communities were randomised to arm A and 5 to arm B. One community withdrew, leaving 5 communities in each group (834 eligible women). Participation was <25%. Using clustered intention-to-treat (ITT) analysis, initial and cumulative averaged uptakes in arm A were 1.4-fold (20% vs 14.3%, p=0.628) and 1.3-fold (20.6% vs 16%, p=0.694) higher compared to arm B, respectively. Corresponding per protocol (PP) analysis indicates 2.2-fold (22.9% vs 10.6%, p=0.305) and 1.6-fold (22.9% vs 14.1%, p=0.448) higher uptakes in arm A compared to arm B. Screening uptake varied between communities (range 0–62.1%). Among women who completed a questionnaire (18.3% in arm A, 21.7% in arm B), the screening uptake was 1.8-fold (ITT; p=0.1132) or 3-fold (PP; p<0.01) higher in arm A versus arm B.ConclusionsPap and HPV self-sampling were compared in a marginalised, Canadian population. Results indicated a preference for self-sampling. More research on how to reach underscreened Indigenous women is necessary.Trial registration numberISRCTN84617261.