BACKGROUND: Positive thinking which is derived from an optimistic view toward the universe and plays an important role in the incidence of better and a more targeted behavior among human beings. It can improve spiritual health in the individuals through increased communication with God and thanksgiving and accelerate the healing process. Accordingly, we aimed to evaluate the effect of positive thinking on the level of spiritual health in the patients with coronary artery disease (CAD) referred to Imam Reza specialty and subspecialty clinic in Shiraz, Iran. METHODS: In this study randomized controlled clinical trial, we enrolled 90 patients with confirmed CAD referred to Imam Reza clinic, Shiraz, during April to July 2013. A blocking randomization method was used to randomize the final 90 participants into intervention (n = 45) and control groups (n = 45). After obtaining written informed consent, the participants were asked to complete two questionnaires. Data were collected using Ellison and Paloutzian’s spiritual well-being scale (SWBS) and a demographic questionnaire. The patients in the intervention group participated in 7 training sessions on positive thinking in which several topics were discussed. The SWBS questionnaire was completed two more times by the participants; once immediately after, and once 1 month after the intervention. 16 patients were excluded from the study due to different reasons, and finally the analysis was performed on 74 patients. RESULTS: The mean ± standard deviation (SD) of spiritual well-being (SWB) increased from 88.71 ± 12.5 to 96.63 ± 12.58 in the intervention group; while, it decreased from 93.19 ± 17.55 to 94.45 ± 16.01 in the control group in the interval of before and 1 month after the intervention. We observed a statistically significant difference between the two groups regarding both variables of time and group (P < 0.001). CONCLUSION: SWB is an important factor which should be considered in the treatment process, and nurses could maintain and improve such dimension of health in the patients through their intervention including drawing the patients’ attention to optimism and positive thinking.