Antidepressants are amongst the very widely prescribed medications in many nations. Researchers have recently studied the association of antidepressants with major adverse cardiovascular events (including death). In a historical study of 1266 patients who completed cardiac rehabilitation in a major center. 433 (34.2%) participants were treated with antidepressants, with the largest proportion of these receiving SSRIs (n = 299; 23.6%). Discontinuation rates ranged from 37.3% for TCAs to 53.2% for SNRIs. After a median follow-up of 4.7 years, 264 (20.9%) participants had a major adverse cardiac event. Those taking tricyclics had significantly more of these events than those not taking TCAs (HR = 2.46; 95% CI 1.37–4.42), and those on SSRI (HR = 1.45; 95% CI 1.07–1.97). The use of all antidepressants except SNRIs was associated with more adverse cardiac events.