Background: Meningococcal disease is characterized by high mortality and risk of serious permanent sequelae among survivors; incidence is highest among infants. We used modeling techniques and secondary data to estimate its annual economic and humanistic burden in the US. Methods: Surveillance data from 1997-2006 were combined with data from epidemiologic, economic, and quality of life studies and public health guidelines to calculate the annual burden of meningococcal disease. Costs included direct medical (vaccination, outbreak prevention, acute treatment, & long-term treatment of sequelae), direct non-medical (special education for patients with permanent sequelae), and lost productivity (due to acute disease, death, and sequelae). The value of lost productivity was calculated with and without inclusion of post-meningococcal disease IQ loss (mean 6.5 points). The humanistic burden was valued in terms of attributable losses in life-years (LYs) and quality-adjusted life-years (QALYs). Costs, LYs, and QALYs were projected to a lifetime horizon based on cases occurring during one year, and discounted to present values at a rate of 3% annually. Results: We estimate the per-case cost of meningococcal disease to be $220,123. Assuming 1,732 annual cases (256 among infants), the aggregate cost of meningococcal disease totals $380 million. Combined with $174 million for routine vaccination, the overall burden is $554 million annually. Including the impact of IQ loss, the cost per case is $ 335,680 and the overall burden $755 million annually. Each case is associated with a loss of 2.9 LYs and 3.9 QALYs. Total LYs and QALYs lost annually due to meningococcal disease are estimated to be 5,023 and 6,755, respectively. Conclusions: Meningococcal disease is associated with a significant economic and humanistic burden in the US. Interventions to improve disease prevention and/or reduce the risks of long-term sequelae may be associated with considerable benefits to patients and payers alike.