Statin-associated muscle symptoms are considered as obvious adverse efects of prolonged statin therapy such as myopathy, myalgia, and rhabdomyolysis. These side efects are associated with vitamin D3 defciency and can be adjusted by amendment of serum vitamin D3 level. Green chemistry aims to decrease the harmful efects of analytical procedures. Here we have developed a green and eco-friendly HPLC method for the determination of atorvastatin calcium and vitamin D3. The two drugs were separated in less than 10 min on Symmetry column C18 (100×4.6 mm, 3.5 µm) using a mixture consisting of 0.1% ortho-phosphoric acid (OPA) (pH=2.16) and ethanol as the mobile phase in gradient manner. We have used Green Analytical Procedure Index (GAPI) tools and the Analytical GREEnness Metric Approach (AGREE) for assessment of the greenness of our proposed method. The method proved linearity over concentration ranges of (5–40) and (1–8) µg/ml with low limit of detection of 0.475 and 0.041 µg/ml for atorvastatin calcium and vitamin D3 respectively. The method was successfully validated in accordance with ICH instructions and utilized for determination of the drugs of interest either in pure form or in their pharmaceuticals