BACKGROUND: Information about life expectancy of patients with homozygous sickle-cell disease is needed for research and patient counselling. Our aim was to study two Jamaican populations, one clinic-based and one birth cohort and, by careful consideration of data quality and statistical analysis, to identify ways to increase the chances of obtaining valid and generalisable results. METHODS: We investigated the survival experience of 3301 patients with homozygous sickle-cell disease attending the Jamaican sickle-cell clinic between Jan 1, 1987, and Dec 31, 1996. We applied and assessed a simulation technique for incorporating early life mortality using a birth cohort, and analysed the precision of this technique. Kaplan-Meier survival estimates are produced. FINDINGS: 290 of the 3301 patients died. Median survival calculated with the excess mortality rate simulation data was 53 years (95% CI 49.3-57.0) for men and 58.5 (55.1-67.5) for women. INTERPRETATION: Our simulation technique, with realistic assumptions based on empirical evidence, offers a new estimate of median survival for patients with homozygous sickle-cell disease. We present the precision of these survival estimates, which introduces an important level of uncertainty. The inherent biases of clinically ascertained populations of patients, and the assumptions underlying analysis techniques are crucial features of survival studies in sickle-cell disease, and can modify summary statistics substantially.