The objective of this study is to evaluate the incidence of pathologic gastroesophageal reflux in laryngectomized patient with phonatory prosthesis, analyzing potential related problems and appraising, at the same time, the effectiveness of a therapeutic protocol. A retrospective study was conducted on 43 phonatory prosthesis patients who had problems with regard to recurrent tracheoesophageal granulations, the need of frequent prosthesis replacement, within a 3-month period, and unsatisfactory vocal results. Such patients underwent physical examination of the fistula region and of the neopharynx and were submitted to esophagogastroduodenoscopy. Moreover the group of patients underwent a therapeutic protocol and were re-evaluated posttreatment, examining fistula region both on the tracheal side and on the esophageal side through videolaryngostroboscopy. Of the 43 recruited patients 13 (30%) presented tracheoesophageal granulations, 20 (46.5%) unsatisfactory vocal results and 10 (23.5%) frequent prosthesis replacement, within a 3-month period, due to abnormal biofilm development. In particular, of the 13 patients who had recurrent granulations, the evaluation results revealed the presence of gastroesophageal reflux disease (GERD) in 6 cases (46%). In the group of patients presenting unsatisfactory vocal results GERD was shown in 13 cases (65%). In the third group of patients GERD was found in two cases (20%). The overall analysis of the data gathered, allowed to identify GERD in 21 (49%) of the 43 patients submitted to the study. The results posttreatment indicated, in the first group, the disappearance or a significant (>75%) volume reduction of such formation in five cases (38%, p = 0.002). In the second group an overall improvement in the quality of voice was displayed at least for 12 patients (60%, p = 0.0001). Finally in the last group an increase of the prosthesis life was recorded in four (40%, p = 0.05) of the ten patients who had the need of prosthesis replacement within 3 months. Also the 22 GERD negative cases (51%) underwent the treatment, therefore representing the control group, whose posttreatment results showed substantial modifications in just two cases (9%). The data obtained suggest a high degree of correlation between the presence of pathologic gastric reflux and the partial or total prosthesis failure. The introduction of a specific therapeutic protocol has allowed to improve the quality of prosthesis (QoP) in 22 of the 43 patients (p < 0.001) who had a pathologic condition of the fistula and of the prosthesis.