Background: We compared the efficacy of two viral hepatitis B and C (VHBC) screening strategies, relative to no intervention, among underprivileged people (UP) living in shelters in the Lyon area., Methods: Eighteen of 37 shelters were randomly sampled after stratification based on the accommodation capacity and the screening centres/shelters distance. Through randomization, the S0 strategy (no intervention), the S1 strategy [group information (GI) and referral for screening] and the S2 strategy (GI and in situ screening) were each applied in six shelters. A standardized questionnaire was offered to each participant. Follow-up of positive cases was organized via the reference centre of VHBC of Lyon., Results: The screening completion rate (SCR) among 1276 included subjects in S0, S1 and S2 was 1.5, 42.8 and 59.7%, respectively (P < 10(-6)). This rate was higher in S2 regardless of the sociodemographic variable considered. Odds ratios (OR) of screening completion (SC) was significantly higher in S1 versus S0, OR = 49.8 [95% confidence interval (CI): 26.1-102.1], in S2 versus S0, OR = 98.5 (95% CI: 51.9-200.8) and in S2 versus S1, OR = 2.0 (95% CI: 1.3-2.9). Age, country of birth and professional inactivity were independently associated with SC., Conclusions: Health authorities must ensure widespread screening of UP, which is more effective when conducted in shelters than in screening centres.