Description: Background: To analyze the impact of multimorbidity (MM) on health care costs taking into account data heterogeneity. Methods: Data come from a multicentre prospective cohort study of 1,050 randomly selected primary care patients aged 65 to 85 years suffering from MM in Germany. MM was defined as co-occurrence of 〉=3 conditions from a list of 29 chronic diseases. A conditional inference tree (CTREE) algorithm was used to detect the underlying structure and most influential variables on costs of inpatient care, outpatient care, medications as well as formal and informal nursing care. Results: Irrespective of the number and combination of co-morbidities, a limited number of factors influential on costs were detected. Parkinson's disease (PD) and cardiac insufficiency (CI) were the most influential variables for total costs. Compared to patients not suffering from any of the two conditions, PD increases predicted mean total costs 3.5-fold to approximately [euro sign] 11,000 per 6 months, and CI two-fold to approximately [euro sign] 6,100. The high total costs of PD are largely due to costs of nursing care. Costs of inpatient care were significantly influenced by cerebral ischemia/chronic stroke, whereas medication costs were associated with COPD, insomnia, PD and diabetes. Except for costs of nursing care, socio-demographic variables did not significantly influence costs. Conclusions: Irrespective of any combination and number of co-occurring diseases, PD and CI appear to be most influential on total health care costs in elderly patients with MM, and only a limited number of factors significantly influenced cost.Trial registration: Current Controlled Trials ISRCTN89818205