Abstract Background Severe mental health disorders directly affect quality of life but may also indirectly relate to physical diseases and their prognosis. We test this hypothesis for the specific case of acute myocardial infarction (AMI), postulating a longer in-patient stay and an excess in-hospital mortality among patients suffering psychiatric comorbidities (PC). Methods A retrospective observational study was conducted using secondary data from public Portuguese hospitals, for all patients with a primary diagnosis of AMI (12,213 patients aged 18-80, for the years 2017-18). We used linear and logistic regression to model length of stay (LoS) and in-hospital mortality, respectively. Having at least one psychiatric comorbidity was the explanatory variable, and models were adjusted for age, sex, and the Charlson Comorbidity Index. Results The prevalence of PC was 12.95%. The in-hospital mortality rate was significantly higher in the group with PC (4.43%, OR = 1.372, 95%CI=1.041-1.784), than in the group without PC (3,38%). Stays were significantly longer among those with PC (mean=7.69 days), compared to those without PC (mean=6.87 days; adjusted β-coefficient=0.098, 95%CI=0.056-0.141). Conclusions Patients with AMI and comorbid mental disorders have poorer hospitalization outcomes than those without PC. This emphasizes the importance of promoting effective management strategies for comorbid psychiatric disorder, for instance, by improving the integration of mental health care in general hospitals, and empowering healthcare professionals to recognize and manage patients with PC. Key messages • Psychiatric comorbidity is related to longer inpatient stays and higher mortality risk among patients with AMI. • Efforts to integrate mental health care in general hospitals should be maintained.