Abstract Background/aim Statin intolerance is increasingly recognized as a therapy limiting factor in the primary and secondary prevention of cardiovascular disease. Since vulnerability to dose related adverse events differ between subjects treated with statins we hypothesized low-dose simvastatin would be tolerated and effective in statin-intolerant patients. Method A single center open label prospective observational study was performed assessing tolerability and efficacy of low-dose simvastatin treatment in 35 statin-intolerant patients. Statin intolerance was defined as not being able to tolerate a registered dose statin due to myalgia–myopathy, myositis, or elevation of serum liver enzyme levels. These statin-intolerant patients were treated with simvastatin with an initial dose of 2.5 mg every other day. The dose was titrated upwards if possible. Tolerability was defined as remaining on treatment. Efficacy was defined as change of LDL-cholesterol compared to baseline. Results The reached simvastatin dose ranged from 0.825 to 8.75 mg/day with a mean dose of 4 mg/day. Fifty-seven percent of the patients tolerated low-dose therapy and remained on treatment. Of these patients, 30% noted recurrent myalgia. Low-dose simvastatin significantly decreased mean(SD) LDL-cholesterol levels with 25.9(12.1)% ( p < 0.001). Eleven percent of the patients reached LDL-cholesterol target levels (< 2.6 mmol/l) in an intention to treat analysis and in 20% of patients that tolerated low-dose simvastatin. Conclusion Low-dose simvastatin therapy is tolerated in a considerable proportion of statin-intolerant patients with significant lipid lowering efficacy. Low-dose statin therapy can be considered in multidrug regimens in statin-intolerant patients.