Objective: The present study aimed to understand the medication status of subjects participating in oral anticancer drug clinical trials, analyze the issues and influencing factors during the medication process, and propose better management approaches for subsequent clinical trials.

Methods: The study included subjects enrolled in oral anticancer drug clinical trials conducted in a cancer hospital in China from 2010 to 2022. We collected general information of the included subjects and the trials and reviewed the distribution and return documentation as well as diary cards of the subjects’ medications. Specific issues occurring during the medication process were analyzed, and the subjects’ medication compliance was estimated. The chi-square test or Pearson’s correlation analysis was performed on medication information, subjects’ basic information, and specific issues encountered by the subjects. Linear regression was used for attribution analysis of specific issues encountered by the subjects during the medication process.

Results: Thirty-two clinical trials on oral anticancer drugs conducted between 2010 and 2022 and involving 700 subjects were reviewed. Among these, 217 subjects experienced loss of medicine, missing dose, overdose, or nonreturn of trial drugs during the medication process in the clinical trial. A total of 93.2% of the medication cycles had 80–120% compliance. Multiple linear regression analysis revealed that sex, number of medication cycles, trial initiation time, and different types of trial drugs were the factors that affected the number of medication issues encountered by the subjects.

Conclusions: Approximately one-third of the subjects participating in oral anticancer drug clinical trials experienced loss of medicine, missing dose, or overdose during the medication process, and the medication issues varied across the different medication periods. The medication compliance of the subjects was good; however, there were still issues such as missed medication during the medication process. Targeted evaluation and monitoring approaches should be established for different experimental categories, subject gender, and medication duration, and effective management measures should be introduced to minimize medication issues during drug clinical trials.