Provided herein is a method of preparing a bile acid derivative using a continuous flow reaction. When bile acid derivatives are synthesized using a continuous flow reaction according to the present invention, the reaction is very safe compared to an existing batch-type reaction, the reaction time is significantly reduced, and high-quality bile acid derivatives may be synthesized with high efficiency. In particularly, according to the present invention, a hydrogenation reaction proceeds under substantially water-free reaction conditions, and thus the conversion rate (UDCA: CDCA) of a UDCA hydrogenation reaction may be significantly enhanced.