Background: Tracheoesophageal speech with a voice prosthesis is considered the rehabilitation treatment of choice in laryngectomized patients. The main reasons for prosthesis failure are endoprosthetic leakage and periprosthetic leakage. The Provox XtraSeal® stent incorporates an additional double flange on the esophageal side to prevent periprosthetic leakage. The objective of this study is to compare the duration and costs of the Provox Vega® and Provox XtraSeal® prostheses used in these patients in a tertiary university hospital. Materials and methods: A prospective crossover case study of laryngectomees with Provox Vega® who underwent Provox XtraSeal® placement due to recurrent periprosthetic leaks and decreased theoretical prosthesis life. The duration and possible factors affecting voice prostheses were studied using Kaplan–Meier curves and Cox regression. A cost-effectiveness analysis was carried out from the perspective of the Spanish National Health System with an incremental cost-effectiveness calculation. Results: A total of 38 patients were recruited, 35 men and 3 women, with a mean age of 66.26 ± 9.36 years old. Information was collected from 551 voice prostheses, 484 Provox Vega® and 68 Provox XtraSeal®. The mean duration of Provox Vega® was 119.75 ± 148.8 days and that of Provox XtraSeal® was 181.99 ± 166.07 days (p = 0.002). The most frequent reason for replacement was endoprosthetic leakage in both groups: 283 (60.86%) in the case of Provox Vega® and 29 (48.33%) in that of XtraSeal® (p < 0.000). To obtain no cost differences (ICE ~ 0) between Provox Vega and Provox XtraSeal, the latter should cost EUR 551.63. Conclusions: The Provox XtraSeal® is a cost-effective option in patients with increased prosthesis replacements due to periprosthetic leakage, reducing the number of replacements, increasing the duration of the prosthesis, and providing savings compared to Provox Vega®.