Introduction: The aim of the study was to investigate the prevalence and risk factors of muscle complications among patients using statins. Methods: We conducted a prospective comparative study on 345 patients receiving statins and compared the findings with an age‐ and gender‐matched control group of 85 subjects. Univariate and multivariate analyses with logistic regression models were used to study the association of different patient and disease characteristics with muscle complications. Results: Adverse reactions were reported by 21% of patients and 5.9% of controls (P = 0.0013). Objective weakness was found in 15% of the patients who reported muscle symptoms (3.2% of the total cohort), but not in controls. Older age, longer duration of statin use, diabetes, stroke, and lower body mass index were associated with increased risk of developing these symptoms. Conclusions: Adverse reactions to statins may be more common than previously reported, and they may be affected by specific patient and disease characteristics. Muscle Nerve 2011