Background and Aim: Statins (HMG-CoA reductase inhibitors) are the "gold standard" for the management of hypercholesterolemia. Although well tolerated by most patients, concerns have been raised regarding statins' safety due to statin associated myopathy (SAM), leading to poor compliance and drug discontinuation. SAM is attributed to environmental and genetic factors, including the T521C single nucleotide polymorphism (SNP) in SLCO1B1. This study aimed to investigating the association between the SLCO1B1 "C" risk allele with SAM in a cohort of Syrian patients on atorvastatin. Study Design and Methods: This case-control observational study encompassed 67 patients receiving atorvastatin, 26 patients who experienced SAM, with/without elevated serum creatine kinase (CK), and 41 SAM-free controls. Patients in both groups were genotyped via sequencing of specific polymerase chain reaction (PCR) amplicons containing the SLCO1B1 SNP. Frequencies of alleles and genotypes were calculated and data were analyzed using SPSS (version 26). Results: The frequency of the SLCO1B1 "C" risk allele was 21.2% and 8.5% in the cases and controls, respectively, and with a statistically significant difference (p= 0.032). The majority of patients were wild type (TT) (65.4% versus 82.9%, p= 0.19) followed by the heterozygous (TC) (26.9% versus 17.1%, p= 0.55), in cases and controls, respectively. The CC homozygote genotype was limited to only two SAM cases (7.7%) (p= 0.026). Genotypes were in accordance with Hardy Weinberg equilibrium in both cases and controls (p= 0.189 and p= 0.513, respectively). No associations were found between SAM and any of non-genetic factors (age, sex, BMI, smoking, and atorvastatin dose). Conclusions: This current study proves high frequency of the SLCO1B1 "C" risk allele in Syrian patients who experienced SAM compared to controls, and supports an involvement of the CC genotype, but not the non-genetic factors, in increasing the susceptibility to SAM.