Background Certain subgroups have higher rates of false fecal immunochemical test (FIT) results, yet few studies have addressed this topic. Objective To identify demographic factors associated with false-positive and false-negative FIT results in colorectal cancer screening. Design Retrospective database review of prospectively collected data. Setting A bowel cancer screening center in Hong Kong invited participants for colorectal cancer screening (2008-2012). Patients Study participants who underwent both FIT and colonoscopy in the first year (n = 4482) and underwent colonoscopy after negative FIT results for 3 consecutive years (n = 857). Main Outcome Measurements The diagnostic accuracy and predictive values of FIT according to participant characteristics. Results The sensitivity, specificity, positive predictive values, and negative predictive values for advanced neoplasia were 33.1%, 91.9%, 19.0%, and 96.0%, respectively. Participants 66 to 70 years of age had higher sensitivity, whereas older age, smoking, and use of aspirin/nonsteroidal anti-inflammatory drugs were associated with lower specificity. The rates of false-positive and false-negative results were 8.1% and 66.9%, respectively. Older age (66-70 years; adjusted odds ratio AOR 1.95; 95% confidence interval CI, 1.35-2.81; P  < .001), smoking (AOR 1.68; 95% CI, 1.08-2.61; P  = .020), and the presence of polypoid adenoma (AOR 1.71; 95% CI, 1.14-2.57; P  = .009) were associated with false-positive results. Younger participants (AOR for elderly participants 0.31) and the use of aspirin/nonsteroidal anti-inflammatory drugs (AOR 4.44) in participants with 1 FIT with negative results and the absence of high-grade dysplasia (AOR for presence 0.41) were associated with false-negative results. Limitations Self-referred participants who received one type of qualitative FIT. Conclusion These findings could be used to target screening more toward those with a higher risk of false-negative results and those with a lower risk of false-positive results for earlier colonoscopy.