Objective: To evaluate the efficacy and safety of Tongfu powder for external application on Shenque (the umbilicus, hereafter, Tongfu powder) versus mosapride in acute pancreatitis (AP) patients with gastrointestinal dysfunction. Methods: A total of 102 AP patients were diagnosed using the latest Atlanta Criterion and recruited at the Department of Infectious Disease, Beijing Friendship Hospital (Beijing, People's Republic of China) from August 2014 to December 2016. Patients were randomized into the Tongfu powder group and mosapride group using the random table. Information on scores (eg, the gastrointestinal function score) on days 1 and 7 of hospitalization, biochemical indicators (eg, interleukin [IL]-2 and IL-6), indicators for curative effects (eg, first defecation time, bowel sound recovery time, hospitalization costs, and duration) were collected and compared between the 2 groups. Results: The gastrointestinal function score decreased significantly after treatment, and the changes were significantly different between the Tongfu powder group and the mosapride group (P<0.05). Significantly shorter time to first defecation and bowel sound recovery was observed in the Tongfu powder group versus the mosapride group (P<0.05). The improvements of IL-2, I L-4, intestinal fatty acid binding protein, motilin, and vasoactive intestinal peptide in the Tongfu powder group were higher than those in the mosapride group (P<0.05). There were no significant differences in hospital cost and length of hospital stay between the 2 groups. Conclusion: This study suggested that Tongfu powder for external application may improve gastrointestinal function for AP patients compared with mosapride.