Objective:Object To evaluate the therapeutic effectiveness of postoperative adjuvant mitotane therapy in the context of adrenocortical carcinoma (ACC) by using a meta-analysis methodology.Methods:A comprehensive literature review was conducted by systematically searching the PubMed, EMBASE, Web of Science, and Cochrane Library databases. The search spanned from the establishment of each database to October 2023. Search terms, "mitotane", "adrenocortical carcinoma" or synonyms. Inclusion criteria, Studies comparing outcomes (overall survival (OS) and/or recurrence-free survival (RFS)) in ACC patients with or without mitotane, reporting adjusted hazard ratios (HR) in multivariate Cox regression. Exclusion criteria, Patients with distant metastases, RI(Microscopic residual tumor) rection of ACC, or adjuvant chemotherapy. Data extracted on mitotane treatment concentration, duration, and tumor stage. A meta-analysis was conducted utilizing R4.2.2 software to assess the impact of ACC on OS or RFS through the calculation of HR and 95% confidence intervals (CI). Subgroup analysis of RFS was conducted based on the use of mitotane to reach effective levels or adequate duration, as well as tumor stage ≤T 3. Results:A meta-analysis was conducted, including a total of 15 studies and involving 2084 patients with ACC. Of these patients, 991 received post-surgical treatment with mitotane, while 753 had ACC classified as stages ≤T 3. The results showed that adjuvant mitotane therapy in the ACC group after surgery led to significantly improved OS ( HR=0.45, 95% CI 0.34-0.58, I2=0, P=0.79) and RFS ( HR=0.65, 95% CI 0.51-0.83, I2=76%, P<0.01) compared to non-adjuvant mitotane therapy. Subgroup analysis further revealed that patients with effective mitotane concentration or sufficient time after surgery[Subgroup a(Median follow-up duration < 45 months): HR=0.59, 95% CI 0.44-0.79, I2=0, P=0.38; Subgroup b(Median follow-up duration ≥ 45 months): HR=0.93, 95% CI 0.90-0.96, I2=0, P=1.00 ]and with ≤T 3 stage ACC ( HR=0.61, 95% CI 0.47-0.79, I2=0, P=0.62)had better RFS compared to those who did not achieve the requisite mitotane concentration or postoperative interval, as well as patients with stage T 4 ACC. Conclusions:The administration of adjuvant mitotane therapy following ACC resection has been shown to significantly extend patients' OS and RFS, particularly when the therapy achieves optimal concentration or is administered for an adequate duration. Furthermore, in patients with ACC classified as stage ≤T 3, the effect of adjuvant mitotane therapy on prolonging RFS appears to be more consistent and reliable.