AIM To determine whether capsaicin infusion could influence heartburn perception and secondary peristalsis in patients with gastroesophageal reflux disease(GERD). METHODS Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air in 10 patients with GERD. In a first protocol, saline and capsaicincontaining red pepper sauce infusions were randomly performed, whereas 2 consecutive sessions of capsaicin-containing red pepper sauce infusions were performed in a second protocol. Tested solutions including 5 m L of red pepper sauce diluted with 15 m L of saline and 20 m L of 0.9% saline were infused into the mid-esophagus via the manometric catheter at a rate of 10 mL /min with a randomized and doubleblind fashion. During each study protocol, perception of heartburn, threshold volumes and peristaltic parameters for secondary peristalsis were analyzed and compared between different stimuli.RESULTS Infusion of capsaicin significantly increased heartburn perception in patients with GERD(P < 0.001), whereas repeated capsaicin infusion significantly reduced heartburn perception(P = 0.003). Acute capsaicin infusion decreased threshold volume of secondary peristalsis(P = 0.001) and increased its frequency(P = 0.01) during rapid air injection. The prevalence of GERD patients with successive secondary peristalsis during slow air injection significantly increased after capsaicin infusion(P = 0.001). Repeated capsaicin infusion increased threshold volume of secondary peristalsis(P = 0.002) and reduced the frequency of secondary peristalsis(P = 0.02) during rapid air injection. CONCLUSION Acute esophageal exposure to capsaicin enhances heartburn sensation and promotes secondary peristalsis in gastroesophageal reflux disease, but repetitive capsaicin infusion reverses these effects.