INTRODUCTION: Patients with lung cancer may present with additional lesions in the central airways. Earlier studies have shown a relationship between vessel diameter, pattern and grade of malignancy. High-definition (HD+) bronchoscopy with image enhancement techniques (i-scan) detected more vascular abnormalities but correlation with pathology has not yet been established. METHODS: In this investigator-initiated, randomised, controlled, crossover, multicentre study in patients with suspected lung cancer, a HD+ bronchoscopy was performed with i-scan1 and i-scan2 settings in random order. Biopsies, visual grade and vascular pattern classification were obtained by endoscopists and blinded evaluation. RESULTS: In 107 patients, vascular patterns were classified in 48 tumours. Abrupt-ending vessels were predominantly found in squamous cell carcinoma but overall correlation between vessel pattern and histology was not significant (p=0.339). Additional lesions were detected in 35 patients (33%) with a correlation between vessel pattern and high-grade (pre-)invasive lesions (p<0.001). In 8.4% of the patients, relevant second lesions were detected which determined treatment and staging in 3% of all patients. Interobserver agreement was excellent for visual grading of the airway epithelium, but low for classifying vascular patterns. No significant detection rate difference was found by blinded and unblinded evaluation. CONCLUSION: HD+ bronchoscopy with i-scan image enhancement readily detects additional lesions. In one-third of all the patients, additional lesions were detected. Their vascular pattern correlates to pathology outcome, but the interobserver correlation for vascular pattern classification is low. These lesions were relevant in 8.4% and affected treatment and work-up in 3% of the cases. TRIAL REGISTRATION NUMBER: NCT02285426; Results.