There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Dfis poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Dfand analyse its relationship with CAD. We replicated 5 Dfloci and found 4 additional loci with suggestive significance (P< 1e−05) to contribute to Dfvariation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Dfand CAD, and between Dfand myocardial infarction (MI), one of CAD’s fatal outcomes. Fine-mapping of Dfloci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Dfprovides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.