Background: Simvastatin is usually taken in the evening due to the circadian rhythm of hepatic cholesterol biosynthesis. The degree of reduction of low-density lipoprotein cholesterol (LDL-C) and the level of adherence to different administration time remained unknown in the Malaysian population. This study aims to investigate the effect of simvastatin on the percentage changes of lipid profile and the level of adherence to when simvastatin was instructed to be taken at different timing. Methods: Nine primary care health clinics across Malaysia participated in this study. 147 statin-naive subjects were selected through convenient sampling and randomised into one of the three arms (after breakfast, after dinner or before bedtime). Differences on percentage reduction of LDL-C from baseline and level of adherence among the three groups at week-16 were compared. The main outcomes measured in this study were the percentage change of lipid parameters and the percentage of high-adherence (MMAS=8) at week-16. Results: 59.2% of the patients were male. The mean age of the study population was 53.93± 10.85 years. Most of the patients were Malays (69.4%); followed by Indians (22.4%) and Chinese (8.2%). LDL-C decreased from 4.26 (Standard Deviation, SD1.01) to 2.36 (SD0.69)mmol/L at week-16 for patients taking simvastatin before bedtime; an absolute reduction of 44.95%.The differences of LDL-C percentage reduction between three arms were significantly different (p<0.001). The greatest LDL-C reduction was observed when simvastatin was taken before bedtime and revealed 56.2% patients with high-adherence at week-16. Conclusion: Simvastatin showed superior LDL-reduction and higher level of adherence when being instructed to be taken before bedtime