Background & Aims: The risk of developing colorectal neoplasia is not well established among family members of individuals with large adenomas and screening strategies remain under debate in this population. This study aimed at quantifying the risk of colorectal adenomas and cancers using colonoscopic screening in first-degree relatives of patients with large adenomas. Methods: This case-control study was performed in 18 endoscopic units of French non-University Hospitals. A colonoscopy was offered to first-degree relatives of 306 index cases with adenomas ≥ 10 mm, if they were alive, aged 40-75 and could be contacted by the index case. Among 674 relatives meeting these criteria, 168 were examined and matched for age, gender, and geographical area with two controls (n=307). Controls were randomly selected from 1362 consecutive patients aged 40-75 having undergone a colonoscopy for minor symptoms. Results: The overall prevalence of large adenomas was 8.4% and 4.2% in relatives and controls, respectively. Odds ratios (OR) associated with a history of large adenomas in relatives were 2.27 (95% confidence interval [CI]: 1.01-5.09) for cancers or large adenomas and 1.21 (95% CI: 0.68-2.15) for small adenomas, and 1.56 (95% CI: 0.96-2.53) for all colorectal neoplasia. The risk of large adenomas and cancers was higher in relatives of index cases younger than 60 years (OR: 3.82; 95% CI: 0.92-15.87) and when the index case had large distal adenomas (OR, 3.14; 95% CI: 1.27-7.73). Conclusion: First-degree relatives of patients with large adenomas are at increased risk of developing colorectal cancers or large adenomas. This result has implications for screening in this high-risk population.