19 Background: LS is among the most common hereditary cancer (CA) syndromes, underlying 3% cases of colorectal CA (CRC) and 8% CRC <50 yrs. LS patients have a high lifetime risk of CRC which is lowered by intensive colonoscopy surveillance. However, interval CRC can still develop, and adjunctive therapies like ASA and NSAIDs have been recognized for their CP benefits, with 35% risk reduction associated with sustained (>2 yrs) ASA use. Existing data are scarce on uptake of CP in LS pts, as well as patient-level factors that may impact uptake. Methods: PREVENTLynch recruited LS participants in the FoxChase Cancer Center (FCCC) Risk Registry, who were invited to complete a one-time e-survey after providing informed consent (1/2020-6/2020; IRB 20-8014). This survey was additionally provided online (PREVENTLynch-II) to US and international patients through 2 patient advocacy websites (10/2022-7/2023). Demographic/personal/familial CA history were collected. Perceived inconvenience, side effects, reassurance, and likelihood of recommending available and emerging CA prevention modalities were measured on 9-point scales (low=1; high=9). Results: 296 patients with LS completed the survey. Median age was 53 yrs [IQR 44-62], and overall CP use was 37.5%. No significant variation in CP uptake was seen based on race, age, marital status or geographic region (nationally and internationally). Personal history of cancer was reported by 56.4%, but was not associated with CP (p=0.6). Gene mutated (MLH1, MSH2, MSH6, PMS2) was not associated with CP (p=0.5).CP users vs non-users perceived greater convenience (mean 1.32 vs 1.90 respectively, p=0.02), lower concern for side effects (2.30 vs 3.61, p=0.0008), and higher perceived preventive reassurance from CP use (5.68 vs 3.93 p<0.0001). CP users were more likely to recommend CP to others (7.57 vs 4.49, p<0.0001). Conclusions: CP uptake is low among patients with LS. Patient perceptions of CP convenience, side effects and preventive benefits predicted CP uptake whereas factors such as age, sex, geographical location, gene affected and personal history of malignancy did not. This suggests a critical need for education addressing negative perceptions of CP among LS patients to improve CP uptake. [Table: see text]