Objectives: This study sought to assess the incidence, procedural characteristics, contributing factors, and clinical outcome of cryoballoon-based pulmonary vein isolation (CB-PVI)–related hemoptysis in a multicenter study. Background: Hemoptysis has been described as a rare complication of CB-PVI. However, the precise mechanism and the etiology of this complication are poorly characterized. Methods: Consecutive patients undergoing CB-PVI for paroxysmal or persistent atrial fibrillation at 4 German hospitals were included in this observational analysis. Results: A total of 4,331 CB-PVI procedures were performed between 2006 and 2019. Fifteen patients (9 men, mean age 68.1 ± 9.8 years) developed acute hemoptysis during or within 24 h after CB-PVI, resulting in a hemoptysis frequency of 0.35%. Hemoptysis occurred in 6 of 720 procedures using the first-generation CB (0.83%) and in 9 of 3,611 procedures using the second-, third-, or fourth-generation CB (0.25%) (p = 0.015). Bronchoscopy was performed in 8 patients and showed bleeding exclusively due to mucosal injury or due to a coagulum at a bronchus adjacent to the ablation site. Hemoptysis resolved spontaneously without any long-term sequelae in all patients, except for a 92-year-old patient who died 13 days after CB-PVI due to pneumonia. No specific endobronchial treatment was necessary. Conclusions: Acute hemoptysis after CB-PVI is a rare but potentially life-threatening complication that is usually self-limiting. Direct thermal injury of bronchi adjacent to a pulmonary vein seems to be the most likely mechanism.