CONTEXT: Several prior studies have found that women are less likely to be screened for colorectal cancer (CRC) than men. While the source of this screening differential is unknown, recent studies suggest gender differences in barriers to screening might explain the disparity. OBJECTIVE: This formative study was designed to explore CRC screening barriers, attitudes and preferences by gender. METHODOLOGY: Focus group interviews with groups stratified by gender and screening status. Participants included 27 females and 43 males between the ages of 50 and 75 years who receive primary care at the Minneapolis VA Medical Center. We conducted interpretive and grounded text analysis of semi-structured focus group interviews to assess how knowledge, experiences and sociocultural norms shape female and male preferences and barriers to current CRC screening guidelines. RESULTS: Female and male participants reported similar preferences for CRC screening mode, but there were notable differences in the barriers and facilitators to screening. Key findings suggest that women viewed the preparation for endoscopic procedures as a major barrier to screening while men did not; women and men expressed different fears and information preferences regarding endoscopic procedures; and women perceive CRC as a male disease thus feeling less vulnerable to CRC. Gender-specific barriers may explain women's lower rate of screening for CRC. CONCLUSION: Colorectal cancer screening promotion interventions, decision aids and clinical practice may benefit by being tailored by gender.