The most effective and acceptable ways of approaching relatives of identified probands to participate in research are unknown. We report on two methods. A total of 640 probands with Crohn's disease were contacted by post and invited to select how the research team would contact their relatives to assess their interest in participating in prevention research. Clinician-led approach: required probands to provide contact details for their first-degree relatives so that the research team could send them study questionnaires; proband-led approach: required probands to request questionnaires with stamped envelopes for them to forward to their relatives. Fifty-six percent (356/640) of probands contacted participated, with 80% (284) providing details of eligible relatives. Forty-eight percent (136/284) of probands requested 392 relatives be contacted by the researchers and 50% (142/284) requested that the questionnaire be sent to them so that they could give this to their 437 relatives personally. Two percent (6/284) requested mixed methods. Eligible responses came from 73% of relatives (587/805), 81% (299/368) of those contacted by the researchers and 66% (288/437) of those contacted via probands (difference 15%, 95% CI 10, 22). Both methods yielded similarly high levels of interest from relatives in participating in prevention research (89% (265/299) direct; 86% (248/288) indirect). Direct clinician-led contact maximised response rates. High levels of interest in research across the two recruitment methods suggest that although proband-led methods may maximise privacy, they may deny relatives the opportunity to take part in research that would be of interest.