Background: To evaluate the frequency, presentation, and course of the acute chest syndrome (ACS) in adult Afro-Caribbean patients with sickle cell disease (SCD). Patients and Methods: Retrospective cohort study during a 12- year period in patients with SCD at least 14 years of age, discharged with a diagnosis of ACS from the only hospital on the Caribbean island of Curacao, where 109 patients with SCD (62 HbSS, 47 HbSC) were observed. Results: Eighty-one episodes of ACS occurred (57 in 34 patients with HbSS and 24 in 19 patients with HbSC). The risk (odds ratio, 1.80; P=.13) and incidence (7.6 vs 4.2 per 100 patient-years P>.2) of ACS did not differ between patients with HbSS and HbSC, but recurrent ACS affected patients with HbSS more (odds ratio, 2.96; P=.09). Abnormal chest sounds (mainly bilateral crepitations) were found in 91% of cases at diagnosis, but 48% had normal chest roentgenograms at that time and had delayed development (5.4 ± 3.4 days) of radiologic abnormalities. Patients with HbSS and HbSC had similar clinical presentations. Mortality (6%) and hospital stay (20 days) were not influenced by the use of transfusions or anticoagulation. All five nonsurviving female patients with HbSS had had more previous admissions for SCD and ACS. Conclusions: Acute chest syndrome occurs in 42% of adult Afro-Caribbean patients with SCD; patients with HbSS are more prone to recurrences. Delayed development of radiologic infiltrates is common. Interventions apart from supportive care do not influence the course of ACS. Fatal ACS occurs in patients with a more severe form of SCD.