© 2015, BMJ Publishing Group. All rights reserved. Objectives: To investigate the relationship between multimorbidity and healthcare utilisation patterns among the highest cost patients in a large, integrated healthcare system. Design: In this retrospective cross-sectional study of all patients in the U.S. Veterans Affairs (VA) Health Care System, we aggregated costs of individuals' outpatient and inpatient care, pharmacy services and VA-sponsored contract care received in 2010. We assessed chronic condition prevalence, multimorbidity as measured by comorbidity count, and multisystem multimorbidity (number of body systems affected by chronic conditions) among the 5% highest cost patients. Using multivariate regression, we examined the association between multimorbidity and healthcare utilisation and costs, adjusting for age, sex, race/ethnicity, marital status, homelessness and health insurance status. Setting: USA VA Health Care System. Participants: 5.2 million VA patients. Measures: Annual total costs; absolute and share of costs generated through outpatient, inpatient, pharmacy and VA-sponsored contract care; number of visits to primary, specialty and mental healthcare; number of emergency department visits and hospitalisations. Results: The 5% highest cost patients (n=261 699) accounted for 47% of total VA costs. Approximately twothirds of these patients had chronic conditions affecting ≥3 body systems. Patients with cancer and schizophrenia were less likely to have documented comorbid conditions than other high-cost patients. Multimorbidity was generally associated with greater outpatient and inpatient utilisation. However, increased multisystem multimorbidity was associated with a higher outpatient share of total costs (1.6 percentage points per affected body system, p<0.01) but a lower inpatient share of total costs (-0.6 percentage points per affected body system, p<0.01). Conclusions: Multisystem multimorbidity is common among high-cost VA patients. While some patients might benefit from disease-specific programmes, for most patients with multimorbidity there is a need for interventions that coordinate and maximise efficiency of outpatient services across multiple conditions.