Background <p>Gastrointestinal stromal tumors (GIST) are rare malignancies originating from mesenchymal tissue, with imatinib as the standard postoperative adjuvant therapy, especially for high-risk patients. However, recurrence after discontinuation remains an important clinical problem. This study aimed to identify factors influencing recurrence after imatinib discontinuation in intermediate- and high-risk GIST patients to guide individualized treatment strategies.</p> Methods <p>Patients who underwent surgical resection and imatinib adjuvant therapy in Nanjing Drum Tower Hospital from 2011 to 2021 were retrospectively analyzed. In this study, end-point of tumor treatment ( EOOT ) recurrence-free survival ( RFS ) was used as the primary endpoint, which was defined as the time from the end of imatinib adjuvant therapy to the recurrence or metastasis of GIST. Univariate and multivariate Cox regression analyses, along with Kaplan-Meier curves, were used to assess the impact of clinicopathological factors.</p> Results <p>Among 82 patients who discontinued imatinib, 19 experienced recurrence. Tumor site, tumor size, mitotic index, Ki-67 index, risk classification, and mutation type were significantly associated with recurrence (<i>P</i> &lt; 0.05). Kaplan-Meier analysis showed that non-gastric tumors, larger size, high Ki-67, and mitotic index were linked to poorer EOOT RFS. In addition, while the EOOT RFS of patients who had been on the drug for more than 3 years was not statistically significantly different from those who had been on the drug for a shorter period of time, overall the RFS after discontinuation was longer in patients who had been on the drug for a longer period of time.</p> Conclusion <p>Tumor size, mitotic index, Ki-67 index, and mutation type are key factors influencing recurrence after imatinib discontinuation. Prolonging the time of adjuvant therapy has an important prognostic improvement effect on high-risk patients.</p>