The acceptability of colorectal cancer (CRC) screening tests to the population influences adherence. Population preferences between fecal occult blood test (FOBT) and colonoscopy for CRC screening were examined by previous test experience. The study population was a random sample of 413 members of Israel's largest Health Maintenance Organization (HMO) aged 48-68 years. In a telephone interview, an explanation was provided regarding FOBT and colonoscopy. Participants were asked which they preferred and their degree (1-6) of agreement with each of eight test characteristics. Overall Attitude Scores toward FOBT and colonoscopy were compared. Predictors of colonoscopy preference and of refusal to undergo screening were examined using a logistic regression model. FOBT was preferred as a screening test by 70.2% of the participants, colonoscopy by 9.3%, 7.4% were indecisive, and 13.1% were not interested in screening. FOBT and colonoscopy similarly scored highly as life saving (5.2 vs. 5.1, respectively), with colonoscopy scoring significantly higher as time consuming (3.8 vs. 1.3, P<0.0001), disturbing (4.6 vs. 1.8, P<0.0001), painful (4.1 vs. 1.0, P<0.0001), annoying (4.8 vs. 1.9, P<0.0001), and involving risk (3.2 vs. 1.0, P<0.0001). In a logistic multivariate analysis, preference of colonoscopy was associated with the perception of being at CRC risk [odds ratio (OR): 3.1 (95% confidence interval (CI): 1.3-7.6)], with more positive attitude scores towards this test [OR: 2.2 (95% CI: 1.6-3.0)], and with a more negative one toward FOBT [OR: 0.4 (95% CI: 0.3-0.7)]. Target population preferences for CRC screening supports a policy of FOBT screening for an average risk population and colonoscopy for high-risk individuals.