BackgroundTracheoesophageal speech is one of the most effective method used for voice rehabilitation after laryngectomy. The main limitation is the need for periodic voice prothesis (VP) replacements. The process of developing VP usage complications is still unexplored. The aim of this study was to assess the level of cytokines (IL‐1β, IL‐6, IL‐8, IL‐10, TNFα) and pepsin in saliva as potential factors reducing VP longevity.MethodsProspective double‐blind randomized clinical trial was conducted (NCT04268459). Patients were randomly divided into two groups depending on VP replacement regimen (regular—every 3 months, or irregular—when complications occur). Levels of IL‐1β, IL‐6, IL‐8, IL‐10, TNFα, and pepsin in saliva samples (fasting and after eating) of laryngectomized patients were measured using ELISA tests.ResultsFifty‐two patients (26 in both groups) with control group (7 patients) participated in the study. The level of IL‐1β, IL‐6, IL‐8, IL‐10, TNFα, and pepsin did not differ according to regularity of VP replacements (p = 0.301–0.801). IL‐6 levels were significantly higher when VP complications occurs (p = 0.012).ConclusionsThe saliva components were not significantly different depending on the frequency of VP replacements. IL‐6 plays an important role in the development of VP use complications.