OBJECTIVES: Medication compliance is critical to the outcome of clinical trials in determining the drug's efficacy. It supports the internal validity of the result of clinical trial and may affect the analysis of the results. The objective of this study was to assess the compliance in clinical trials, compare with the result of the previous research, search factors that affect the compliance and present the management plan for those of poor compliance. METHODS: Compliance rate was analyzed for 658 subjects who were included in 22 clinical trials at a clinical trial center in Gyeonggi-do, Korea from January 2007 to September 2010. Compliance assessed by pill counts and rates greater than 80% to 100% were defined as adequate compliance and its affecting factors were analyzed RESULTS: Overall compliance rate was 87.3±24.1%, the proportion of the adequate compliance accounted for 53.8%. There is no difference in average compliance by gender, but female rates higher than male in the adequate compliance. The average compliance tended to increase with age and the maintenance rate that means the percentage of ongoing patient in clinical trials. Simplifying dosing regimen and adding the number of visit improve compliance too. Visit intervals, total days of taking medication, medication package and the design of clinical trials with placebo do not affect the compliance. Patients with Alzheimer's disease, cancer, hypertension and stroke are more likely to comply to their medication regimen than those with other disease CONCLUSIONS: There are several factors affecting compliance in clinical trials. Age, maintenance rate, simple dosing regimen, number of visit and certain disease improve medication compliance in clinical trials. These factors should be applied to clinical trials when planning the process of the trials. It will be needed to assist patients to follow medication prescriptions during clinical trials by motivational strategies and active intervention