Statins are the most commonly prescribed treatment in the UK. Recently updated NICE guidelines have lowered the threshold for statin use to include all patients with a 10% or greater 10-year risk of cardiovascular disease. Previous randomised trials have established the prevalence of serious adverse effects of statins such as rhabdomyolysis, however, many patients discontinue statins due to less severe symptoms, such as muscle pain or fatigue. Randomised trials have shown no differences between those taking statin and placebo in terms of the prevalence of these side effects (approximately 9%), but currently there is no pathway of care for clinicians to empirically and objectively evaluate whether symptoms reported by a statin-user are caused by the statin itself or the so-called ‘nocebo’ effect (symptoms reflecting patient expectation of side effects). Given the effectiveness of statins in preventing cardiovascular disease, accurate data on the cause of symptoms experienced during statin use are needed to reliably inform patient and clinician about continuation of use. The proposed StatinWISE trial will provide definitive answers to this important uncertainty about statin therapy.