To study the safety and efficacy of Sanhuang Qingwei pill in the treatment of peptic ulcer (PU) with cold-heat-intertwisting syndrome. Methods: Ninety four patients with PU with cold-heat-intertwisting syndrome from June 2013 to December 2013 were selected and randomly divided into control group (47 cases) and observation group (47 cases). Patients in the control group received standard triple therapy while patients in the observation group received Sanhuang Qingwei pill combined with standard triple therapy. Before and after treatment of 4 weeks, the short-time and long-time effect and adverse reaction were compared between two groups. Results: After treatment of 4 weeks, the cure rate was 65.96% and the total effective rate was 93.62% in the observation group, which was significantly higher than those 51.06% and 82.98% of the control group (P<0.05); the eradication rate of Hp of observation group by 14C-DPM were significantly higher than that of the control group (P<0.05); the cure rate and total effective rate were significantly higher than those in the control group (P<0.05); the rate of adverse reactions and recurrence of the observation group were significantly lower than those of the control group (P< 0.05). Conclusion: Compared with the triple therapy, treatment of PU with cold-heat-intertwisting syndrome by Sanhuang Qingwei pill can improve clinical effect and reduce incidence of adverse reactions. This method is worth promoting in clinical practices.