This study aimed to estimate the incidence of gastrointestinal symptoms (GIS) and associated factors in an outpatient cohort of people living with HIV/AIDS (PLWHA) followed between October 2009 and July 2011. We evaluated nausea and/or vomiting, dyspepsia, heartburn, diarrhea, constipation, and flatulence. The outcome variable was the presence of three or more GIS. Sociodemographic (sex, skin color, age, income, years of schooling), lifestyle (smoking status, alcohol consumption, physical activity level), clinical (antiretroviral therapy, time of HIV infection, CD4 lymphocyte count, viral load), and anthropometric (nutritional status and waist circumference) variables were investigated. Data on sociodemographic and lifestyle variables were collected through a pre-tested and standardized questionnaire. CD4 count was determined by flow cytometry and viral load by branched DNA (bDNA) assays for HIV-1. All variables were analyzed at a p<0.05 significance level. Among 290 patients, the incidence of three or more GIS was 28.8% (95% CI 23.17 to 33.84) and 74.48% presented at least one symptom. Female gender (IR 2.29, 95% CI 1.63 to 3.22) and smoking status (IR 1.93, 95% CI 1.30 to 2.88) were risk factors for the presence of three or more GIS after multivariate Poisson regression. A high incidence of gastrointestinal symptoms was found among PLWHA, and it was significantly associated with female sex and tobacco use. Those results reinforce the relevance of investigating the presence of GIS in PLWHA as it may affect treatment adherence.