Background <p>Using the fecal immunochemical test (FIT) with risk factors for advanced colorectal neoplasia (AN – the combination of colorectal cancer and advanced precancerous polyps) could improve the yield of colonoscopy in both screening and diagnostic settings. In this systematic review, we evaluated: (1) yield and efficiency of FIT alone vs. FIT plus risk factors for screening and among FIT positive individuals; (2) study quality for these two settings.</p> Methods <p>Following literature searches of Ovid MEDLINE and Embase from January 2010 to March 2026, two reviewers independently identified published English-language studies that evaluated FIT performance with and without risk factors among average-risk adults aged ≥ 40 years undergoing screening colonoscopy and among FIT positive subjects, independently extracted descriptive and numerical data, and evaluated study quality. We compared colonoscopy yield and efficiency of FIT alone versus FIT with risk prediction models and risk factors in screening and diagnostic studies.</p> Results <p>From 1891 articles, we identified 9 screening studies and 10 diagnostic studies for a positive FIT. Both groups of studies were homogeneous in design and of good quality. In the nine screening studies, age, sex, BMI, family history of CRC, and smoking were most often used with varying model metrics and varying degrees of discrimination, and with modest-to-moderate improvements in efficiency at the cost of missing a proportion of AN. Among the ten diagnostic studies, the combination of fecal hemoglobin, age, sex, and smoking had the greatest improvement on yield and efficiency, but also missed a small proportion of AN.</p> Conclusions <p>In the screening setting, the yield of colonoscopy for AN improves when risk factors are used to stratify who is first screened with FIT vs. colonoscopy. In the diagnostic setting, risk factors help prioritize FIT-positive patients for diagnostic colonoscopy because of high risk for AN.</p>