Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that imposes a great burden on the patient, the patient's family and society. However, we lack information about the total disease burden at a national level, especially regarding costs before and after diagnosis and the consequences for spouses. We aimed to estimate the factual direct and indirect costs of ALS in a national sample. Using records from the Danish National Patient Registry (1998-2009), 2,394 patients with ALS were identified and subsequently compared with 9,575 randomly chosen control subjects matched for age, gender and geographic area/civil status. Direct costs, including frequencies of primary and sector contacts and procedures, and medication from primary and secondary sectors, were obtained from the Danish Ministry of Health, the Danish Medicines Agency, and the National Health Security. Indirect costs included labour supply and social transfer payments, and were based on income data derived from Coherent Social Statistics. Patients with a diagnosis of ALS had poor survival. The average (95 % CI) 5-year survival rate was 0.278 (0.358-0.298) compared with 0.865 (0.858-0.872) among controls. Patients with ALS had significantly higher rates of health-related contact and medication use and higher socioeconomic costs. They also had very low employment rates, while those in employment had a lower income level than control subjects. The annual mean excess health-related cost was 18,918 for each ALS patient. However, spouses showed no excess health usage; in fact, their employment and income rates were higher, and the net cost was reduced by -3,420. We conclude that ALS has serious mortality, health and socioeconomic consequences for patients. However, the consequences for spouses are complex; they tend to compensate for the social consequences to patients by increasing their net income after ALS diagnosis.