Introduction: Cirrhosis of liver carries multiple clinical morbidities; portal Hypertension, Minimal and overt Encephalopathy, renal Insufficiency, Esophageal and rectal Varies, Small bowel Ischemia, ascetics and constipation. Usage of lactulose to regulate bowel movements was optimal to relief constipation lowering Encephalopathy. Disaccharides cause Glucose Intolerance and Diarrhea depleting electrolyte provoking Hepato Renal Syndrome. Rifaximin is the standard of care for MHE or OHE, further precipitates constipation. Plecanatide is a natural Uroguanyle Agonist without systemic Absorption, a Ph dependent drug for constipation with minimal side effects. This clinical study evaluates the efficacy of Plecanatide in compensated cirrhosis. Methods: The total study population (n = 60) comprised of Sixty Compensated cirrhotics with a mean MELD 0f 8 were randomized in two groups: A (Lactulose 30 cc Bid with Rifaximin 550 mg BID for 12 weeks) and B (Plecanatide 3 mg orally plus Rifaximin 550 mg bid for 12 weeks). All groups had a washout time two weeks from all existing medications for Constipation or Enemas or Suppository. The daily diet contained Total 3000 cal/day, Total protein 150 gm/day (vegetable), Total Fat 30 gm/day, Total fiber 100 gm/day, Total salt of 2 grams and total fluid 1000cc. All HE was measured by Flicker test and Trial Test Block test. Satisfactory Bowel Movement score was calculated for all the patients (0 - dissatisfactory, 4 -Satisfactory). Modified QOL was obtained. (0-Poor, 1- Good, 2 & 3 - Very good, 4 - Excellent) Exclusion Criteria: Renal failure, TIPS, HCC, post-Transplant, sepsis, HRS, CHF, IBD, Dialysis, Severe Ascites, Uncontrolled DM Cardiac Arrhythmia, BMI Drugs: Calcium Blocker, Anticholinergic medication, Herbal and OTC for Constipation, Miralax, suppositories, Enema, Prostaglandin analogs and other prescription drugs for constipation. Patient Characteristics: Table1 Results: Primary endpoint: Complete Spontaneous Bowel Movement (CSBM) in 24 hours Secondary endpoint: Sustained bowel movement post 12 weeks Table 2 Side Events Table 3 Conclusion: Clinical pilot reveals higher Efficacy of Plecanatide on Complete Spontaneous Bowel movements and Sustained Bowel Movements without drop out. No difference in regard to Overall HE in both groups. Large cohort studies required to validate.910_A Figure 1 No Caption available.910_B Figure 2 No Caption available.910_C Figure 3 No Caption available.