Singleton pregnancies with ICP in five tertiary medical centers were randomly divided into three treatment groups: oral UDCA 4× 250 mg daily (Group 1, n= 41), intravenous SAMe 1000 mg daily (Group 2, n= 38), and a combination of both drugs (Group 3, n= 41) until delivery. Paired t test, analysis of covariance and non-parametric test were used. All therapies significantly and equally improved pruritus. The serum levels of total bile acids (TBA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TB) in each group significantly decreased after treatment (p< 0.05). Group 1 was more effective than Group 2 in reducing TBA concentration (p< 0.05), Group 1 and Group 3 showed more effective than Group 2 in reducing AST and TB concentrations (p< 0.05), and Group 1 facilitated deliveries at term. No perinatal death or adverse drug reactions were observed. UDCA and SAMe are both effective and safe in the treatment of ICP. UDCA monotherapy should be used as the first line therapy for ICP because it is more efficacious, cost-effective and convenient.