Objective: To compare symptoms, signs, and acoustical voice quality changes throughout the 6-month course of empirical treatment between laryngopharyngeal reflux (LPR) males and females. Materials and Methods: Forty clinically diagnosed LPR females and 40 males with a reflux finding score (RFS) > 7 and a reflux symptom index (RSI) > 13 were treated with pantoprazole and diet recommendations during 3 or 6 months according to their evolution. RSI, RFS, and acoustic parameters were assessed at baseline and 3 and 6 months posttreatment. A correlation analysis between videolaryngostroboscopic findings and acoustic measurements was performed. Results: RSI, RFS, and many acoustic measurements (i.e., percent jitter, percent shimmer, phonatory fundamental frequency range, fundamental frequency variation , and peak-to-peak amplitude variation) significantly improved from baseline to 3 months posttreatment in male group. In female group, RSI and RFS total score significantly improved along the 3 first months of treatment. However, some clinical outcomes (i.e., RSI total score, hoarseness, cough, and globus) continued to improve from 3 to 6 months of treatment. We did not identify significant improvement of acoustic measurements in female group. The correlation study did not reveal significant correlation between videolaryngostroboscopic findings and acoustic measurements. Conclusion: This preliminary study suggests the occurrence of gender-related differences in the LPR therapeutic response. Further studies need to clarify whether females require a longer course of therapy than males.