This study aimed to examine the associations between perceived health status and spiritual well-being and rational drug use among individuals with cardiovascular disease in Turkey. The study was conducted with the participation of 261 individuals diagnosed with cardiovascular disease who received inpatient treatment at a university hospital in a province in the Central Black Sea Region. Data in the study were collected using a participant information form, the Rational Drug Use Scale, the Health Perception Scale, and the FACIT-Sp Spiritual Well-Being Scale. In this study, patients' perceived health and spiritual well-being positively influence rational medication use. In the multivariate linear regression analysis, after controlling for sociodemographic and clinical variables, the model was statistically significant and explained 55.5% of the variance in rational drug use.