Introduction: Vocal fold leukoplakia (VFL) has a risk of malignant transformation, and the underlying mechanisms are currently unrecognized. Some clinical evidence has indicated that laryngopharyngeal reflux (LPR) probably plays a critical role. Objective: To explore the risk factors associated with the occurrence of VFL and to investigate the importance of LPR in VFL and its different pathological types using 24-h multichannel intraluminal impedance-pH monitoring. Materials and Methods: Eighty-one patients with VFL and 27 healthy volunteers were recruited. General information and LPR parameters were analyzed. Results: The monitoring showed that 35.8% (29/81) of patients had acidic LPR and that 43.2% (35/81) had weakly acidic LPR. Heavy drinking (odds ratio = 4.004, p = 0.037) and acidic LPR (odds ratio = 4.471, p = 0.029) were independent risk factors for the occurrence of VFL. Acidic LPR showed a strong correlation with the Reflux Finding Score (p < 0.05) in patients suspected of having LPR based on the scale score. Meanwhile, weakly acidic LPR parameters increased with the severity of pathological degrees which were higher in high-grade dysplasia (p < 0.05). Conclusion: Our study confirms the importance of LPR in VFL. Heavy drinking patients with VFL, particularly those with acidic LPR, should undergo intensive treatment. Meanwhile, weakly acidic LPR may play a critical role in the pathological changes in VFL.