Abstract Background Intensive care units represent one of the largest clinical cost centers in hospitals. Mechanical ventilation accounts for a significant share of this cost. There is a relative dearth of information quantifying the impact of ventilation on daily ICU cost. We thus determine daily costs of ICU care, incremental cost of mechanical ventilation per ICU day, and further differentiate cost by underlying diseases. Methods Total ICU costs, length of ICU stay, and duration of mechanical ventilation of all 10,637 adult patients treated in ICUs at a German hospital in 2013 were analyzed for never-ventilated patients (N = 9181), patients ventilated at least 1 day, (N = 1455) and all patients (N = 10,637). Total ICU costs were regressed on the number of ICU days. Finally, costs were analyzed separately by ICD-10 chapter of main diagnosis. Results Daily non-ventilated costs were €999 (95%CI €924 - €1074), and ventilated costs were €1590 (95%CI €1524 - €1657), a 59% increase. Costs per non-ventilated ICU day differed substantially and were lowest for endocrine, nutritional or metabolic diseases (€844), and highest for musculoskeletal diseases (€1357). Costs per ventilated ICU day were lowest for diseases of the circulatory system (€1439) and highest for cancer patients (€1594). The relative cost increase due to ventilation was highest for diseases of the respiratory system (94%) and even non-systematic for patients with musculoskeletal diseases (13%, p = 0.634). Conclusions Results show substantial variability of ICU costs for different underlying diseases and underline mechanical ventilation as an important driver of ICU costs.