A prospective cohort study to assess the risk factors for acute chest syndrome (ACS) in individuals with sickle cell disease was carried out in a referral center from Sergipe, Brazil. A total of 168 SS homozygotic individuals (ages between 12 wk and 26 y) were followed for 12 months. There were 134 admissions of 81 patients. There were 50 events of ACS, which was the second most frequent cause of hospital admission (after pain crisis). One patient died of ischemic stroke during follow up. In bivariate analysis, the following variables showed statistically significant associations with the occurrence of ACS: age less than 5 years, living in rural area, history of previous hospital admission; white blood cell count greater than 10,000/dL; hemoglobin concentration less than 7 g/dL and oxygen saturation ≤ 95% on admission. After controlling for confounding in multivariate logistic regression, only a history of previous admission remained as an independent predictor of ACS (relative risk=4.20; 95% confidence interval: 1.79-9.87; P=0.001). Patients with a positive history of hospital admission are under increased risk and should be monitored closely for prevention and early detection of ACS.