Inclusion Criteria:  Participants must have a diagnosis of phenotypic FAP with disease involvement of the duodenum and rectum as defined by:  Genetic diagnosis: APC germline mutation (with or without family history) or obligate carrier. Clinical diagnosis: FAP phenotype with >100 adenomas in large intestine and participant has a family history of FAP. Clinical diagnosis: FAP phenotype who are status post colectomy for polyposis, participant has a family history of FAP, and 2 FAP experts agree to the diagnosis. Attenuated FAP diagnosis: APC germline mutation required. Participants must have no evidence of active or recurrent invasive cancer for 6 months prior to screening and must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation). Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of OCA in participants <18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable. ECOG performance status ≤1 (Karnofsky ≥70%; see Appendix A) Participants must have normal organ and marrow function as defined below:  Hemoglobin >10 g/dL or Hematocrit > 30 % Leukocyte count ≥3,500/microliter Platelet count ≥100,000/microliter Absolute neutrophil count ≥1,500/microliter Creatinine clearance (calculated if measured is not available) ≥60 mL/min/1.73m2  AST (SGOT)/ALT (SGPT) ≤2 times the institutional upper limit of normal (ULN) Total bilirubin ≤1.5 the ULN; participants with Gilbert's disease may be enrolled with higher Total bilirubin if their Direct bilirubin is ≤ 1.5 times the ULN.  Presence of Spigelman stage II or III duodenal polyposis at screening  Presence of intact rectum or ileo-rectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA) Willing and able to adhere to the prohibitions and restrictions specified in the final approved protocol The effects of OCA on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. Ability to understand and the willingness to sign a written informed consent document.  Exclusion Criteria:  Prior use of study drug Duodenal or rectal/pouch polyp burden that is not quantifiable Histologically-confirmed high-grade dysplasia or cancer on biopsy at screening Individuals with active, known or suspected chronic liver disease including cirrhosis, nonalcoholic steatohepatitis with liver fibrosis, NASH with cirrhosis, primary sclerosing cholangitis, biliary atresia Individuals with acute cholecystitis (defined by a syndrome of right upper quadrant pain, fever, and leukocytosis associated with gallbladder inflammation diagnosed within the prior 6 weeks) or biliary obstruction (defined by extrahepatic cholestasis) Individuals with hyperlipidemia not well controlled with the use of pharmacotherapy and/or dietary modifications History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof. Pregnant, breast-feeding, or women of childbearing potential unwilling to use a reliable contraceptive method. Pregnant women are excluded from this study because OCA is an agent with unknown effects on the developing human fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OCA, breastfeeding should be discontinued if the mother is treated with OCA. Known hypersensitivity, allergies, or intolerance to the study drug or compounds of similar chemical or biologic composition. Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures. Participants may not be receiving any other investigational agents. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.  Individuals taking the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 5 half-lives days prior to starting OCA or placebo on this study. Consultation with the participant's primary care provider may be obtained but is not required. The use of the following drugs or drug classes is prohibited during OCA/placebo treatment:  Investigational agents; Bile acid sequestrants (bile acid binding resins): cholestyramine, colestipol, or colesevelam Bile salt efflux pump (BSEP) inhibitors Clozapine Theophylline derivatives Tizanidine Warfarin