Multiple system atrophy and progressive supranuclear palsy are disabling neurodegenerative disorders, also known as atypical parkinsonian syndromes. Currently, no health economic evaluations of these diseases are available. The objective of this study was to evaluate disease-related costs in German patients with multiple system atrophy and progressive supranuclear palsy and to identify cost-driving factors. We recruited 101 consecutive patients with multiple system atrophy (n = 54) and progressive supranuclear palsy (n = 47) in four German specialised movement disorder clinics. The health economic data were collected using comprehensive health economic questionnaires ("bottom-up" approach). Costs were calculated from the societal perspective in 2010 Euros. Independent cost-driving factors were identified in multiple regression analysis. The total semi-annual costs of atypical parkinsonian syndromes were EUR 16,670 (95% CI: 13,470-21,850). Direct costs accounted for 73% (inpatient care 31%, special equipment 24%, copayments of patients 21%, others 24%) and indirect costs for 27% of total costs. The economic burden imposed on patients by atypical parkinsonian syndromes accounted for 36% of their income. Independent cost-driving factors were younger age, disease severity, living without a partner and depression. The disease-related costs of atypical parkinsonian syndromes in Germany are high and above the costs reported for idiopathic Parkinson's disease. Disease-specific patterns of cost distributions in atypical parkinsonian syndromes and independent cost-drivers should be considered in future health economic evaluations and healthcare programs. The early diagnosis and treatment of depression in patients with atypical parkinsonian syndromes as well as programs aimed to improve social support will reduce disease-related costs.