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Background: The diagnosis of acute chest syndrome (ACS) in sickle cell disease (SCD) presents an important challenge to the physician. It may present insidiously and non-specifically, often complicating other conditions. It is a frequent pulmonary complication of SCD and the major cause of hospitalization and mortality, accounting for 25% of deaths in patients with sickle cell disease. This syndrome is multifactorial in nature with underlying factors including fat embolism, bone infarction and infection with a wide range of organisms. Methods and Materials: This was a retrospective cohort study done over 1 year period from 1st March 2014 – 28th February 2015 with an aim to study the clinical spectrum, laboratory findings, the precipitating factors and the outcome. Patients were divided into three groups on the basis of age (>12 -20 years, 21–40 years, >41 -60 years) with a view to assess the above parameters. Observations: Of the total of 75 patients with sickle cell anaemia, there were 23 presentations of acute chest syndrome. Male to female sex ratio was 1:2. 78.3% of the patients were admitted for vaso-occlusive crisis (pain crisis) and developed ACS after hospital admission. The commonest clinical presentation were fever and dyspnoea (21.7%) in the patients of ≥12 to 20 years age group while those in the age group of 21 to 40 years commonly presented with shortness of breath (69.2%) followed by chest pain (56.5%). The commonest physical findings were tachypnoea and tachycardia in both age groups. No clinical finding was predictive of the severity of hypoxia. Infection was found to be the triggering factor in 8.6% of the cases. The average duration of crisis was 7.2 days (SD ± 2.53), while the mean length of hospitalization was 9.53 days. 3 (13.04%) patients required invasive ventilation. There were 2 deaths giving rise to the mortality of 8.7%. Conclusion: ACS is an important cause of morbidity in sickle cell disease patients. The diagnosis can be challenging to the physicians due to its elusive nature. Clinical manifestations vary widely. It frequently complicates unrelated hospital admissions and hence the need for strict vigilance so that early management can be instituted and morbidity and mortality can be limited