AIMS: Death of a spouse from acute myocardial infarction (AMI) presents hardship, yet few studies have investigated the psychological consequences of fatal and non-fatal AMI on spouses. METHODS AND RESULTS: Several Danish national registries were linked to identify individuals whose spouses had a fatal or non-fatal AMI. Married patients with fatal or non-fatal AMI (1997-2008) were matched with their counterparts dying or hospitalized with a non-AMI cause; incident use of antidepressants and benzodiazepines, incident depression care, and suicides were compared pre- and post-event using Poisson models. Overall, 16 506 spouses of individuals dying of AMI were matched with 49 518 spouses of individuals dying of a non-AMI cause. Similarly, 44 566 spouses of individuals with a non-fatal AMI were matched with 131 563 spouses of individuals with a non-fatal, non-AMI hospitalization. Those whose spouse died of AMI (compared with a non-AMI cause) had increased antidepressant and benzodiazepine use [peak incidence rate ratio (IRR) 5.7 vs. 3.3, and 46.4 vs. 13.0, respectively; P< 0.001]. Those whose spouse had a non-fatal AMI (compared with a non-AMI hospitalization) had increased risk for antidepressant and benzodiazepine initiation (IRR 1.5 vs. 1.1, and 6.7 vs. 1.3, respectively, P< 0.001). Spouses of fatal AMI patients also had an increased risk of depression and suicide. Male individuals whose spouse had a fatal or non-fatal AMI had a relatively higher increased risk of depression than female individuals. CONCLUSION: Spouses of those who experience AMIs-both fatal and non-fatal-are at elevated risk for psychological consequences; therefore, the care needs of AMI patients and their spouses need to be considered.