INTRODUCTION: Chagas disease, caused by the parasite Trypanosoma cruzi , affects more than seven million people worldwide and it is considered by the World Health Organization (WHO) a neglected tropical disease (1). About one third of Chagas patients develop gastrointestinal disorders, such as dysphagia and achalasia. Management of the disease focuses on symptom improvement and drugs that relax the lower esophageal sphincter pressure (LESP), such as isosorbide and nifedipine. However, the use of these therapies is doubtful because of their side effects and palliative approach (2). The objective of this systematic review is to assess the effectiveness of isosorbide and nifedipine on gastrointestinal manifestation of Chagas disease. METHODS: We searched MEDLINE, EMBASE and LILACS databases to retrieve potentially relevant articles from inception to December 2016. Inclusion criteria: clinical trials, cohorts or cross-sectional design; adults (>18 years old); assessment of effects of isosorbide or nifedipine on gastrointestinal symptoms in Chagas patients. Two reviewers independently screened titles and abstracts, selected eligible studies and extracted data from each study. PROSPERO registration number: CRD42017055143. RESULTS: Eight studies were included (two case series, two clinical trials and four crossovers). Three studies evaluated the effect of isosorbide in LESP and three in esophageal emptying. All of them found that isosorbide rapidly reduces LESP and increases esophageal emptying rates, improving dysphagia. However, several patients reported collateral effects, such as gastroesophageal reflux, headaches and dizziness. One study evaluated the effect of nifedipine on LESP and one on esophageal emptying. Nifedipine decreased LESP, but there was no effect on esophageal emptying. CONCLUSIONS: The available evidence shows isosorbide is effective in the management of gastrointestinal symptoms. Frequently health care of Chagas disease patients is delivered by primary care physicians. So, information on effectiveness of interventions can be aggregated to clinical guidelines, having an important value to inform general practitioners on the decision-making process regarding treatment of this group of patients, avoiding referencing to a specialized care.