Introduction: Limited data exist on colonoscopy after abnormal fecal immunochemical test (FIT)-DNA (a.k.a. multitarget stool DNA test). We hypothesized that endoscopists perform a more careful exam (e.g., longer withdrawal time (WT)) and recommend early re-screening after FIT-DNA+/negative colonoscopy due to expectations about test performance. We aimed to A) determine adenoma detection rate (ADR) and other lesion detection rates and B) assess endoscopist behavior regarding WT and recommendations after negative colonoscopy for 3 indications: 1) FIT-DNA+, 2) average-risk screening (SCR) and 3) abnormal fecal occult blood test (FOBT+, guaiac or FIT). Methods: Using GIQuIC data (2019-2022) from 727 endoscopy units, we identified patients aged 50-75 years undergoing colonoscopy for FIT-DNA+, SCR or FOBT+. We excluded colonoscopy with any other indications (e.g., family history), inadequate bowel preparation or incomplete exam. If pathology was obtained but results were not available, the record was excluded from pathology-related outcomes. Generalized estimating equations clustered by endoscopist were used to assess the association between indication and outcomes while adjusting for patient characteristics and endoscopist's screening ADR. Results: >1.8 million colonoscopies were included; demographics varied by indication (Table). FIT-DNA+ was associated with higher ADR (59.6%) than SCR (39.3%, p< 0.0001) and FOBT+ (53.8%, p< .0001) and greater detection of advanced neoplasia and sessile serrated lesions (Table). Among those with no pathology obtained on colonoscopy, WT was longer for FIT-DNA+ than for SCR and FOBT+. Among patients aged 50-65 years with no pathology and ASA < IV, a 10-year colonoscopy was recommended in only 80.1% of FIT-DNA+ patients vs. 87.2% of SCR and 86.5% of FOBT+. In multivariable models, compared to FIT-DNA+, SCR and FOBT+ are associated with shorter WT (p< 0.0001 for both), and lower odds of adenoma detection (OR 0.48 (95% CI 0.47-0.50) and 0.71 (0.68-0.74), respectively) and recommendations for re-screening in < 10 years (OR 0.64 (0.57-0.72) and 0.84 (0.74-0.96), respectively). Conclusion: FIT-DNA+ is associated with greater neoplasia detection than FOBT+ and SCR, but also with longer WT and more recommendations for early re-screening after a negative colonoscopy. Despite lower specificity of FIT-DNA vs. FOBT, endoscopists seem to have greater concern for missed pathology in FIT-DNA+/negative colonoscopies, leading to downstream impacts on healthcare utilization. Table 1. - Colonoscopy for Abnormal FIT-DNA vs. Average Risk Screening vs. Abnormal FOBT:Patient Characteristics, Findings and Follow-Up Recommendations After a Negative Exam FIT-DNA+(n=23,046) Average Risk Screening(n=1,760,840) FOBT+(n=26,455) Age, mean (sd) 64.2 (7.1) 58.7 (7.2) 63.8 (7.2) Male (%)Female (%) 9,939 (43.1)13,107 (56.9) 816,630 (46.4)944,210 (53.6) 12,698 (48.0)13,757 (52.0) White (%)Black of African American (%)Asian (%)Other (%)Unknown/Declined (%) 15,777 (68.5)1085 (4.7)211 (0.9)514 (2.2)5459 (23.7) 1,022,859 (58.1)171,348 (9.7)56,644 (3.2)68,966 (3.9)441,033 (25.1) 16,387 (61.9)2112 (8.0)959 (3.6)1224 (4.6)5773 (21.8) Non-Hispanic (%)Hispanic/Latino (%)Unknown/Decline 14,234 (61.8)560 (2.4)8252 (35.8) 1,018,724 (57.9)107,147 (6.1)634,969 (36.1) 16,691 (63.1)2407 (9.1)7357 (27.8) Total endoscopists contributing colonoscopies 2650 4845 3223 Endoscopist mean ADR‡(sd) with minimum 50 colonoscopies 39.1% (10.2)(Endoscopist n=2467) 39.2% (10.9)(Endoscopist n=3878) 39.5% (10.6)(Endoscopist n=3006) Colonoscopy Findings Adenoma Detection Rate (ADR) 59.6% *,§ 39.3% § 53.8% ADR for Males 67.6% *,§ 46.4% § 61.0% ADR for Females 53.6% *,§ 33.2% § 47.2% Advanced Neoplasia Detection± 22.2% *,§ 7.6% § 17.4% Sessile Serrated Lesion Detection 16.2% *,§ 8.2% † 8.8% Adenocarcinoma Detection 1.5% * 0.3% § 1.4% Analysis of Subgroup with No Polyps on Colonoscopy (i.e., No Pathology Obtained) Median Withdrawal Time, Minutes (interquartile range) (n=4211)8.5 (6.9-11.0) *,§ (n=673,519)7.8 (6.4-9.9) (n=7455)7.8 (6.3-10.1) Next Recommended Colonoscopy (limited to age 50-65, ASA< IV, exclude other or none)< 10 Years (%)10 Years (%) (n=2125)422 (19.9)1703 (80.1) (n=567,568)72,403 (12.8)495,165 (87.2) (n=4301)579 (13.5)3722 (86.5) Next Recommended Colonoscopy (limited to age 50-65, ASA< IV, exclude other or none)≤3 Years (%)4 or 5 Years (%)6-9 Years (%)10 Years (%)Excluded intervals n:OtherNone (n=2125)*,§ 76 (3.6)333 (15.7)13 (0.6)1703 (80.1) 1518 (n=567,568)§ 3840 (0.7)65,289 (11.5)3274 (0.6)495,165 (87.2) 2335974 (n=4301)65 (1.5)478 (11.1)36 (0.8)3722 (86.5) 2919 ‡ADR includes average risk screening only, ages 50-75, photodocumentation of the cecum, adequate bowel preparation.*p<0.0001 compared with average risk screening.§p<0.0001 compared with FOBT+.†p=0.0002 compared with FOBT+. ± Includes either 1) adenoma≥10 mm, with high grade dysplasia, or with villous component; OR 2) sessile serrated polyp (SSP)≥10 mm, SSP with dysplasia, or traditional serrated adenoma; OR 3) adenocarcinoma.