The study aimed to investigate the impact of a spiritual support program on the quality of life of stroke survivors with a history of substance abuse. To achieve this, a randomized controlled trial was conducted at the ICU ward of Imam Khomeini Hospital in Iran. The participants, consisting of 100 stroke survivors who had experienced substance overdose, were randomly assigned to either an intervention group or a control group, with 50 participants in each group. The intervention group received a four-session spiritual support program, while the control group did not receive any spiritual support. The quality of life of the participants was assessed using the Stroke-Specific Quality of Life (SS-QoL) scale at baseline and post-intervention. The results of the study showed that there was no significant difference in the mean quality of life score between the intervention and control groups at the baseline. However, post-intervention, a significant disparity was observed in the mean quality of life score between the two groups. The intervention group demonstrated a significant improvement in the mean quality of life score and its dimensions post-intervention, whereas the control group did not show any significant changes in quality-of-life scores. The study highlights the importance of addressing spiritual needs as part of a holistic, patient-centered care approach to enhance the well-being and recovery of stroke survivors with a history of substance abuse. The findings suggest that a spiritual support program can be an effective way to improve the quality of life for this patient population. The study's protocol was registered at the Thai Clinical Trials Registry (TCTR20250204005), ensuring transparency and accountability in the research process. Overall, the study emphasizes the need for healthcare providers to consider the spiritual needs of their patients, particularly those with complex medical and social histories, to provide comprehensive and supportive care. Link: https://pubmed.ncbi.nlm.nih.gov/40330762/