The choice between the semisitting position (SSP) and the lateral position (LP) for vestibular schwannoma (VS) surgery remains a topic of debate, particularly for large tumors, and high-quality evidence is limited. This study aimed to prospectively determine the optimal surgical position for VS with a diameter of >= 3 cm. This analysis is based on a randomized clinical trial assessing the efficacy and safety of VS surgery in SSP versus LP. Outcomes included the extent of resection, functional results, complications, and health economics. A total of 115 consecutive patients with large VS were prospectively enrolled between December 2019 and November 2023 (SSP: 58, LP: 57). The gross-total resection (GTR) rate was significantly higher in the SSP group compared to the LP group (P = 0.026). There was no significant difference in facial nerve (FN) function between the groups 7 days post-operation; however, FN function was superior in the LP group after 1 year. Preoperative preparation duration and craniotomy durations in the SSP group were significantly longer, while overall operative time, tumor resection, and cranial closure durations showed no significant differences between the groups. In terms of health economics, patients in the SSP group had longer hospital stays and higher hospitalization costs. This study demonstrated that SSP offers advantages in achieving higher GTR rates. However, it does not provide any significant benefit in preserving facial nerve function. Given the elevated risks of VAE, SSP should primarily be considered for patients in good physical condition. Furthermore, patients in the SSP group required more extensive preoperative evaluations and intensive monitoring, resulting in longer hospital stays and increased costs. The financial implications of hospitalization should also be taken into account.