The associations between depression and coronary heart disease, especially via platelet hyperactivity, have been widely described. The relationships between depression and venous thromboembolism are less clear. We present three cases of pulmonary embolism (PE) in patients with previously diagnosed depression and discuss possible, depression-related prothrombotic factors, including the impact of psychotropic drugs. A 69 year-old woman, treated with different antidepressants and also antipsychotics, died two months after recurrent PE. Another woman, at the same age, on mirtazapine therapy, developed segmental PE. In a 39 year-old man, taking paroxetine, severe PE required thrombolysis.