Abstract Funding Acknowledgements None. Background Vitamin D has cardioprotective properties. A status of hypovitaminosis D, defined as vitamin D ≤ 20 ng/ml, was found to have a comparable effect to diabetes mellitus (DM) in terms of adverse outcomes in patients with acute myocardial infarction (AMI). To date, it is known that hypovitaminosis D is more frequent in women than men but there is still a paucity of data on how gender differences in vitamin D levels are associated with the extent of coronary heart disease (CAD). Purpose To evaluate the relationship between vitamin D status on CAD incidence and severity in patients with AMI. Methods Blood samples were obtained from 1484 patients with AMI on hospital admission. Levels of vitamin D ≤ 10 ng/ml were considered as severe hypovitaminosis D. CAD was defined as the presence of at least one coronary vessel stenosis greater than 50%, while severe CAD was defined as left main disease and/or three-vessel disease. The endpoint was all-cause mortality. Results The cohort's mean age was 66.25 (11.47) years, the majority were male (71.8%) and 24.3% of patients had DM. Overall, 86.2% of patients had CAD and 32.9% severe CAD. The median vitamin D concentration was 17.25 [10.3 - 24.7] ng/ml, and 23.6% of patients had severe hypovitaminosis D. In female patients, hypovitaminosis D was significantly more common in whom with severe CAD (74.1% vs 58.1%, p=0.002), but not in men (61.3% vs 57.1%, p=0.193). On the other hand, severe hypovitaminosis D was significantly more frequent in patients with severe CAD in both genders (male and female respectively 26.6% vs 17.9%, p=0.005; 40.5% vs 26.4%, p=0.001). In female patients, severe CAD was predicted by hypovitaminosis D (OR: 1.85 [1.14 – 3.03], p=0.013) along with DM and older age after correction for confounders as GFR<60 mL/min/1.73 m2, higher cholesterol levels and body mass index. However, hypovitaminosis D was not an independent predictor of severe CAD in men. Moreover, a composite of hypovitaminosis D and DM was identified as a predictor of severe CAD when compared to patients with neither hypovitaminosis D nor DM (OR: 3.56 [1.8 – 7.03], p=0.021) only in female patients. Conclusions The identification of an association between hypovitaminosis D and severe CAD in women but not in men is a novelty in this field. Furthermore, we found that the presence of both hypovitaminosis D and DM has a greater contribution to severe CAD in female patients with AMI.