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ObjectivesTo measure the feasibility and effectiveness of interventions to increase cervical screening uptake amongst young women.MethodsA two-phase cluster randomized trial conducted in general practices in the NHS Cervical Screening Programme. In Phase 1, women in practices randomized to intervention due for their first invitation to cervical screening received a pre-invitation leaflet and, separately, access to online booking. In Phase 2, non-attenders at six months were randomized to one of: vaginal self-sample kits sent unrequested or offered; timed appointments; nurse navigator; or the choice between nurse navigator or self-sample kits. Primary outcome was uplift in intervention vs. control practices, at 3 and 12 months post invitation.ResultsPhase 1 randomized 20,879 women. Neither pre-invitation leaflet nor online booking increased screening uptake by three months (18.8% pre-invitation leaflet vs. 19.2% control and 17.8% online booking vs. 17.2% control). Uptake was higher amongst human papillomavirus vaccinees at three months (OR 2.07, 95% CI 1.69–2.53, p < 0.001). Phase 2 randomized 10,126 non-attenders, with 32–34 clusters for each intervention and 100 clusters as controls. Sending self-sample kits increased uptake at 12 months (OR 1.51, 95% CI 1.20–1.91, p = 0.001), as did timed appointments (OR 1.41, 95% CI 1.14–1.74, p = 0.001). The offer of a nurse navigator, a self-sample kits on request, and choice between timed appointments and nurse navigator were ineffective.ConclusionsAmongst non-attenders, self-sample kits sent and timed appointments achieved an uplift in screening over the short term; longer term impact is less certain. Prior human papillomavirus vaccination was associated with increased screening uptake.