To establish a combined classification based on intrapapillary capillary loops (IPCLs) and morphological characteristics to improve the accuracy of pathological prediction of vocal fold leukoplakia (VFL). A prospective research was conducted of VFL patients diagnosed by IPCLs and morphology. The VFL cases were classified as Type I-III based on IPCLs and morphological characteristics. Type I referred to VFL with dendritic vessels but not IPCLs. Type II defined VFL without any IPCLs or vessels and classified by morphology into two subtypes as non-rough Type IIa and rough Type IIb. Type III referred to VFL with IPCLs and classified into two subtypes as Type IIIa with small IPCLs and Type IIIb with large IPCLs or vascular distortion in or around lesions. Predicting pathology accuracy was analyzed. 182 eligible patients were recruited. The prediction accuracy rates of VFL pathology were 81.5% according to the 2019 Ni classification. The combined classification includes 4 cases of Type I, 28 Type IIa, 35 Type IIb, 56 Type IIIa, and 59 Type IIIb VFLs. The prediction accuracy rate of combined classification ranged from 95.1% to 97.3% in three observers. The average sensitivity, specificity, positive predictive value, negative predictive value was 97.8%, 86.2%, 97.4%, 88.2%, respectively. The inter-observer agreement varied from 84.1% to 94.0%, and mean area under curve of receiver-operating curve analysis was 0.954. The new combined classification based on IPCLs and morphological characteristics could predict pathology of VFL accurately. 4 Laryngoscope, 2024.