Background <p>Death anxiety represents a persistent form of anxiety experienced by patients with Myocardial Infarction (MI), even after receiving medical treatment. Recognizing the critical role of self-transcendence in managing emotions and anxiety, this study aims to investigate the relationship between perceived stress and death anxiety with the mediating role of self-transcendence among older patients with MI.</p> Methods <p>This descriptive and correlational study, conducted in 2023, included 252 older patients with MI. Participants were selected through a convenience sampling method. Data was collected using the Templer Death Anxiety Scale, the Cohen Perceived Stress Scale, and the Reed Self-Transcendence questionnaires. Structural equation modeling (SEM) was employed to examine the mediating role of self-transcendence in the relationship between perceived stress and death anxiety.</p> Results <p>The study comprised 252 older patients with a mean age of 66.98 ± 6.92 years. The majority of participants were male (<i>n</i> = 188, 74.6%) and married (<i>n</i> = 191, 75.8%). The mean scores for perceived stress, death anxiety, and self-transcendence were 29.48 ± 4.30, 8.86 ± 3.28, and 41.81 ± 6.29, respectively. The results of SEM analysis revealed a significant association between perceived stress and death anxiety (<i>β</i> = 0.16, <i>P</i> = 0.04), with self-transcendence playing a mediating role (<i>β</i> = 0.20, <i>P</i> &lt; 0.001), in this relationship.</p> Conclusions <p>Based on the mediating role of self-transcendence, clinically, healthcare providers should assess for and facilitate self-transcendent practices as a component of routine cardiac rehabilitation. Policymakers and program directors should fund and integrate evidence-based interventions like meaning-centered psychotherapy or mindfulness-based stress reduction, which are known to cultivate self-transcendence, into standard post-MI care pathways to directly target the reduction of death anxiety.</p>