In nearly 50% of patients with drug-induced liver injury, the bile flow is impaired known as cholestasis. Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease that happens in pregnancy. Some of the clinical symptoms include pruritus, dark urine, and abnormal liver function tests. A rise of serum bile acids is the most accurate diagnostic evidence. ICP may lead to premature birth, fetal distress, and even postpartum hemorrhage or stillbirth in some severe cases. Higher bile acid levels (> 40 μmol/L) are associated with higher rates of adverse fetal outcomes. Due to the multifactorial nature of ICP, its etiology is still not fully understood. Therefore, the current treatments of ICP are limited to control symptoms and protect fetuses. Among various causing factors, drug exposure during pregnancy is one common factor, and it can be prevented if we know drugs with increasing risk of cholestasis. Here we analyzed over 9.5 million FDA adverse effect reports to identify drugs with increasing risks of cholestasis as an adverse effect. Patients treated for cholestasis or liver diseases were removed. The odds ratio analysis reveals that lansoprazole (LSPZ), omeprazole (OMPZ) and amoxicillin (AMXC) are associated with an increased risk of cholestasis. LSPZ is associated with increased reported cholestasis by a factor of 2.32 (OR with 95% confidence interval [2.21, 2.43]). OMPZ is associated with increased reported cholestasis by a factor of 2.61 [2.54, 2.69]. AMXC is associated with increased reported cholestasis adverse effect by a factor of 6.79 [6.49, 7.11]. The risk of cholestasis associated with these three drugs is further increased in pregnant women. These findings justify careful reassessment of the safety of the three identified drugs.