Background Homelessness shares many similarities with other socio-economically deprived circumstances. It was not known whether the health of homeless people was similar to that of other deprived non-homeless populations. Aims To describe hospital admissions and deaths in a cohort of homeless Glasgow adults and to compare these to socio-economically deprived groups within a matched sample of the non-homeless local population. Methods A retrospective 5-year cohort study was conducted comparing an exposed (homeless) cohort of adults with an age and sex matched unexposed (non-homeless) cohort from the local general population. All participants’ linked hospitalisation and death records were identified. Survival was analysed using comparisons of rates, Kaplan-Meier plots and Cox proportional hazards models. Hospitalisation rate ratios were compared using an exact Poisson method. Additional proportional hazards models were produced to adjust for morbidity, which was identified in hospital records up to 5 years before death. Results 6323 homeless and 12 625 non-homeless adults were studied. The mean ages of men and women in both cohorts at entry were 33 and 30 years, respectively, and 65% were men. After 5 years 1.7% of the general population and 7.2% of the homeless population had died. Age and sex adjusted hazards of death, compared with residents of the most affluent areas, were 2.6 (95% CI 1.5 – 4.4) for residents of the most deprived areas and 8.7 (95% CI 5.2 – 14.5) for homeless individuals. Men were at twice the risk of death as women. Homelessness was associated with death on average 12 years younger than the matched general population (41 versus 53 years). A third of deaths in the homeless were caused by drugs and a further 16% by alcohol. In the homeless, adjusted hazards ratios for deaths by drugs were 20.4 (95% CI 12.0 – 34.7), for suicide were 8.4 (95% CI 3.9 – 18.2), for assault were 7.0 (95% CI 2.6 – 19.0) and for alcohol were 4.7 (95% CI 3.1 – 7.1) compared with the non-homeless population. Homelessness remained an independent risk factor for death after adjustment for morbidities, with a hazard ratio of 2.4 (95% CI 1.3 – 4.3) compared with living in the most affluent non-homeless circumstances. Hospitalisation for alcohol related conditions increased the risk of death from alcohol by 42-fold but homelessness added no further hazard. In contrast, hospitalisation for drug-related causes raised the risk of death from them by 4-fold and homelessness added a further 7-fold risk. The risk ratio for emergency hospitalisation in the homeless was 6.4 compared with the non-homeless. Admission rates were higher in the homeless for all conditions except cancers. Risk ratios in the homeless compared to the most affluent non-homeless cohorts were highest for cellulitis (risk ratio 112.9, 95% CI 20.2 – 4472.0), drug poisoning (risk ratio 90.0, 95% CI 16.0 – 3565.9) and convulsions (risk ratio 71.5, 95% CI 12.7 – 2834.1) In men, lengths of stay were longest in patients from the most affluent areas and shortest in the homeless. In women, lengths of stay increased with greater socio-economic deprivation but homeless women had stays that were typical of the general population. There was little difference in elective admission rates across different socio-economic strata. Homelessness was associated with a small reduction in risk of elective hospitalisation in men and a small increase in women compared with the general population. Admissions for treatment of infectious and parasitic disease were 9 times more common in the homeless. Admissions for injuries, poisonings, mental and behavioural disorders, and maternity related diagnoses were around 2-3 more common in the homeless. Homelessness was associated with almost 3-fold increases in elective admissions for abortions but an 80% lower risk of vasectomy. Lengths of stay for elective admissions increased with deprivation and were longest in the homeless. Conclusions The morbidity and mortality of homeless adults is significantly worse than that of the most deprived non-homeless populations of Glasgow. Hospital inpatients who are homeless are at greater risk of death for a number of conditions and may benefit from more intensive treatment and follow-up.