BACKGROUND: Hospital readmissions are common and costly. A recent previous hospitalization preceding the index admission is a marker of increased risk of future readmission. OBJECTIVES: To identify factors associated with an increased risk of recurrent readmission in medical patients with 2 or more hospitalizations in the past 6 months. DESIGN: Prospective cohort study. SETTING: Australian teaching hospital acute medical wards, February 2006-February 2007. PARTICIPANTS: 142 inpatients aged =50 years with a previous hospitalization =6 months preceding the index admission. Patients from residential care, with terminal illness, or with serious cognitive or language difficulties were excluded. VARIABLES OF INTEREST: Demographics, previous hospitalizations, diagnosis, comorbidities and nutritional status were recorded in hospital. Participants were assessed at home within 2 weeks of hospital discharge using validated questionnaires for cognition, literacy, activities of daily living (ADL)/instrumental activities of daily living (IADL) function, depression, anxiety, alcohol use, medication adherence, social support, and financial status. MAIN OUTCOME MEASURE: Unplanned readmission to the study hospital within 6 months. RESULTS: A total of 55 participants (38.7%) had a further unplanned hospital admission within 6 months. In multivariate analysis, chronic disease (adjusted odds ratio [OR] 3.4; 95% confidence interval [CI], 1.3-9.3, P = 0.002), depressive symptoms (adjusted OR, 3.0; 95% CI, 1.3-6.8, P = 0.01), and underweight (adjusted OR, 12.7; 95% CI, 2.3-70.7, P = 0.004) were significant predictors of readmission after adjusting for age, length of stay and functional status. CONCLUSIONS: In this high-risk patient group, multiple chronic conditions are common and predict increased risk of readmission. Post-hospital interventions should consider targeting nutritional and mood status in this population. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.