© 2020 Informa UK Limited, trading as Taylor & Francis Group.Aims: This study aimed to develop a new intelligent diagnostic approach using an artificial neural network (ANN). Moreover, we investigated whether the learning-method-guided quantitative analysis approach adequately described mediastinal lymphadenopathies on endobronchial ultrasound (EBUS) images. Methods: In total, 345 lymph nodes (LNs) from 345 EBUS images were used as source input datasets for the application group. The group consisted of 300 and 45 textural patterns as input and output variables, respectively. The input and output datasets were processed using MATLAB. All these datasets were utilized for the training and testing of the ANN. Results: The best diagnostic accuracy was 82% of that obtained from the textural patterns of the LNs pattern (89% sensitivity, 72% specificity, and 78.2% area under the curve). The negative predictive values were 81% compared to the corresponding positive predictive values of 83%. Due to the application group’s pattern-based evaluation, the LN pattern was statistically significant (p =.002). Conclusions: The proposed intelligent approach could be useful in making diagnoses. Further development is required to improve the diagnostic accuracy of the visual interpretation.