Objectives <p>To evaluate indicators that predict the success of rapid maxillary expansion (RME) in late adolescents using pretreatment cone-beam computed tomography (CBCT).</p> Materials and methods <p>A prospective clinical trial was conducted to integrate radiological and clinical evaluations with blinded outcome assessment. A total of 46 patients (18 males and 28 females) with a mean age of 15.7 ± 1.4 years were enrolled. All patients were diagnosed with posterior skeletal crossbite and underwent CBCT scans prior to rapid maxillary expansion (RME) using a bonded hyrax expander. Patients were divided into Successful (S-RME) or Failed (F-RME) groups based on midpalatal suture response four days after expansion initiation. Expansion was performed twice daily and continued until molar overcorrection, followed by a four-month fixation. Four CBCT variables (midpalatal suture maturation [MSM], Cervical vertebral maturation [CVM], midpalatal suture density [MSD], and the length and thickness of the palate), age, and sex were analyzed using t-tests, Mann-Whitney U, and chi-square. ICC evaluated random errors.</p> Results <p>Age, maturation stage (MSM), CVM stage, MSD, and the length of the palate were all variables with a statistically significant correlation (P &lt;.05). Sex, as well as the thickness and area of the palate, did not show significant differences between the groups (P &gt;. 05).</p> Conclusions <p>Patients with a higher stage of MSM and CVM had a greater risk of RME failure. Additionally, patients with a lower density ratio and shorter palate length had a better prognosis for conventional RME.</p> Clinical Relevance <p>Choosing between traditional and surgically assisted rapid maxillary expansion (RME) is challenging, especially in late adolescents. Orthodontists should consider additional indicators to guide clinical decisions.</p> Clinical trial registration number <p>ISRCTN31077190.</p>