Introduction: Some patients with atrial fibrillation and high stroke risk cannot be anticoagulated. Percutaneous left atrial appendage occlusion (LAAO) is a potential alternative stroke risk reduction strategy. The LAA secretes ANP which has neurohormonal effects on fluid balance, but the effects of LAAO on clinical volume status remains uncertain.Goals: We expanded upon our prior data reporting a rise in diuretic use after LAAO by including a control cohort of patients without LAAO.Methods: Retrospective clinical data from patients who underwent LAAO at our institution from 2015-2020 with Watchman 2.5 (n=151, 38% female) and Watchman FLX patients from 2020-2022 (n=80, 31% female) were analyzed. A control group consisting of patients with atrial fibrillation who have not had LAAO were included (n=186, 38% female). Data extracted included demographics, loop diuretic dose, LVEF, and presence of HTN, CAD, PAD, DM, CKD, TIA/CVA. Progressive volume retention was defined as initiation or increase in loop diuretic dose within 12 months of LAAO, or within last 12 months from most recent cardiology visit for controls.Results: There was no significant difference in clinical variables between the two groups except for a significantly high proportion of TIA/CVA in LAAO group (p=0.003) and CKD and HF in the control group (p=0.031 and 0.004, respectively). Specifically, 49/231 (21.2%) of the LAAO cohort showed a rise in loop diuretic requirements compared to 27/186 (14.5%) of the controls (p = 0.078). There were 17/231 (7.4%) new loop diuretic prescriptions in the LAAO group compared to 6/186 (3.2%) for the controls (p = 0.066). In multivariable analyses controlling for age, sex, BMI, preimplant LVEF, prior HF, CKD, and LAAO, only age, prior HF, and LAAO predicted a rise in loop diuretic in subsequent year after implant. The strongest predictors were the presence of prior HF, OR 2.32 (95% CI 1.28-4.21, p = 0.005) and LAAO, OR 1.9 (95% CI 1.09-3.27, p = 0.023).Conclusions: These results suggest that LAAO is associated with an almost two-fold increased risk of clinically relevant volume retention. This risk appears to be highest among patients with a clinical history of HF. These findings may inform preimplantation discussions and post-LAAO expectations and clinical management.