Objective <p>Although thermal ablation, surgery, and radiotherapy are established locoregional therapies for adrenal metastases, direct comparisons among these treatments are limited. This study aimed to compare the clinical effectiveness and safety of locoregional treatments for adrenal metastases.</p> Materials and methods <p>This multicenter retrospective cohort study included patients with adrenal metastases treated with locoregional therapies, including thermal ablation, surgery, or radiotherapy. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics. Local progression-free survival (LPFS), overall survival (OS), complication rates, and cost were evaluated. Nomograms for OS prediction were developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression models.</p> Results <p>A total of 496 patients (median age, 57 years; 384 men) were included: surgery (<i>n</i> = 231), ablation (<i>n</i> = 132), and radiotherapy (<i>n</i> = 133). After IPTW adjustment, surgery and radiotherapy showed significantly improved LPFS compared with ablation (<i>p</i> = 0.021). Subgroup analysis demonstrated no significant differences in LPFS among treatment modalities for tumors smaller than 5 cm (<i>p</i> = 0.23). Regarding OS, surgery had a significantly better survival compared with ablation and radiotherapy (<i>p</i> = 0.004). Thermal ablation exhibited the lowest complication rates and lowest treatment cost (<i>p</i> &lt; 0.001). The OS nomogram showed moderate predictive ability.</p> Conclusions <p>Locoregional therapy strategies for adrenal metastases should be individualized. For tumors smaller than 5 cm, thermal ablation offers local tumor control comparable to surgery and radiotherapy, while providing superior safety and lower treatment costs.</p> Key Points <p><Emphasis Type="BoldItalic">Question</Emphasis><i>Direct comparative evidence among thermal ablation, surgery, and radiotherapy for adrenal metastases is limited. How do clinical effectiveness, safety, and cost of these treatment modalities compare?</i></p> <p><Emphasis Type="BoldItalic">Findings</Emphasis><i>For adrenal metastases smaller than 5 cm, thermal ablation provides local control comparable to surgery and radiotherapy, while being associated with significantly fewer complications and lower treatment costs</i>.</p> <p><Emphasis Type="BoldItalic">Clinical relevance</Emphasis><i>For patients with adrenal metastases smaller than 5 cm, thermal ablation offers a minimally invasive, safer, and less costly treatment option. It provides local tumor control comparable to surgery or radiotherapy, supporting individualized treatment selection based on tumor size</i>.</p> Graphical Abstract <p></p>