Objective: The objective of the present study is to examine the association between Big Five personality traits and self-rated health (SRH) among individuals with coronary heart disease (CHD), and to compare this relationship with that of healthy control participants, which is of importance as SRH can be a determinant of outcomes. Methods: The current study used data from 566 participants with CHD with a mean age of 63.00 (S.D. = 15.23) years old (61.13% males) and 8608 age- and sex-matched healthy controls with a mean age of 63.87 (S.D.= 9.60) years old (61.93% males) from the UKHLS. The current study used predictive normative modelling approaches, one-samplettests, a hierarchical regression, and two multiple regressions. Results: The current study found that CHD patients have significantly lower Conscientiousness (t(565) = −3.84,p< 0.001, 95% C.I. [−0.28, −0.09], Cohen’s d = −0.16) and SRH (t(565) = −13.83,p< 0.001, 95% C.I. [−0.68, −0.51], and Cohen’s d = −0.58) scores compared to age and sex-matched healthy controls. Moreover, health status (controls vs. CHD patients) moderated the links between Neuroticism, Extraversion and SRH. Specifically, Neuroticism (b = −0.03,p< 0.01, 95% C.I. [−0.04, −0.01]), Openness (b = 0.04,p< 0.001, 95% C.I. [0.02, 0.06]), and Conscientiousness (b = 0.08,p< 0.001, 95% C.I. [0.06, 0.10]) were significant predictors of SRH in healthy controls, whereas Conscientiousness (b = 0.08,p< 0.05, 95% C.I. [0.01, 0.16]) and Extraversion (b = −0.09,p< 0.01, 95% C.I. [−0.15, −0.02]) were significant predictors of SRH in CHD patients. Conclusion: Based on the close associations between personality traits and SRH, and the subsequent impact on patient outcomes, the results of this study should be taken into consideration by clinicians and health professionals when developing tailored treatment and intervention programs for their patients.