Abstract Background and Purpose Statins are essential for managing cardiovascular disease (CVD), yet adverse effects can lead to discontinuation and non-adherence. The UAE’s multiethnic population presents unique challenges for personalized medicine. Pharmacogenomic (PGx) testing could enhance statin efficacy and safety but is not commonly used in clinical practice. This EmHeart Study sub-analysis aimed to assess genetic and demographic factors associated with side effects in rosuvastatin and atorvastatin users among 675 patients, highlighting the need for PGx-guided therapy. Experimental Approach Patients were genotyped for SLCO1B1 and ABCG2 variants using real-time PCR. Data on demographics, comorbidities, and statin use were gathered from electronic records, with side effects tracked over 12 months. Chi-square tests and logistic regression analyzed associations between patient characteristics, genetic variants, and adverse effects. Key Results East Asians with the ABCG2 rs2231142 variant had a threefold increased risk of liver enzyme elevation with rosuvastatin. Atorvastatin users carrying SLCO1B1 rs4149056 had twice the risk of statin-associated muscle symptoms (SAMS), with higher rates in females and Arabs. Additionally, combining rosuvastatin with ezetimibe further increased risks of both SAMS and liver enzyme elevation. Conclusion and Implications Although PGx in statin prescribing is well-studied, it is underutilized in clinical practice. Importantly, genetic factors are not the sole determinants in physician decision-making. This study demonstrates that gender, ethnicity, and genetic testing significantly impact statin choice. Avoiding rosuvastatin in patients with liver-related risks and increasing physician awareness of these risks can optimize efficacy, safety, and adherence across diverse populations