Context: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and is largely preventable with appropriate screening. Modeling estimates for screening found no difference in life-years gained between annual fecal immunochemical tests (FITs) and 10-year-interval colonoscopy. Screening colonoscopy is one of the leading contributors to US health care costs. Fecal immunochemical testing followed by colonoscopy, if positive, is a much less expensive option for CRC screening. There are limited data on the validity of various FITs for detecting advanced colorectal neoplasia (ACN = advanced adenoma or carcinoma). Purpose: To compare the performance of five FIT brands for detecting ACN, using colonoscopy as the gold standard. Methods: Interim analysis of patients aged 50-85 years undergoing screening or surveillance colonoscopy recruited from three academic medical centers in the United States. Each patient completed five FITs on a single stool specimen prior to colonoscopy. FITs were analyzed according to manufacturer instructions and the subsequent colonoscopy and pathology reports were reviewed. Based on colonoscopy results, we calculated the sensitivity, specificity, and predictive values for each FIT. We used PROC GLIMMIX models in SAS to compare sensitivity and specificity across the different brands, accounting for within-patient correlation. Results: For the 2654 participants enrolled to date, the mean (SD) age was 62 (7.8) years, 62% were women, 87% white, and 30% Hispanic. Based on colonoscopy, 205 patients (7.7%) had ACN, including 6 participants (0.2%) with CRC and 199 participants (7.5%) with advanced adenomas. Among the 2654, the positivity rates for each test were 3%, 12%, 16%, 11%, and 6%. The sensitivity for detecting ACN was 7%, 28%, 41%, 35%, and 21%; and the corresponding specificities were 97%, 89%, 86%, 90%, and 95%. Positive predictive values were 17%, 18%, 19%, 23%, and 28%; and the corresponding negative predictive values were 93%, 94%, 94%, 94%, and 94%. We found statistically significant differences in sensitivity (P< .01) and specificity (P<.01) across tests. Conclusion: Preliminary results suggest substantial variation in performance among different FIT brands when used for single-sample stool testing. If confirmed, these differences could impact regulatory policy and FIT brand selection by healthcare providers. Funding: National Cancer Institute 5R01 CA215034 (Levy, PI)