Copyright © 2019 by the American Thoracic Society Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Spirometry loops are not smooth curves and have undulations and peaks that likely reflect heterogeneity of airflow. Objectives: To assess whether the Peak Index, the number of peaks adjusted for lung size, is associated with clinical outcomes. Methods: We analyzed spirometry data of 9,584 participants enrolled in the COPDGene study and counted the number of peaks in the descending part of the expiratory flow–volume curve from the peak expiratory flow to end-expiration. We adjusted the peaks count for the volume of the lungs from peak expiratory flow to end-expiration to derive the Peak Index. Multivariable regression analyses were performed to test associations between the Peak Index and lung function, respiratory morbidity, structural lung disease on computed tomography (CT), forced expiratory volume in 1 second (FEV1) decline, and mortality. Results: The Peak Index progressively increased from Global Initiative for Chronic Obstructive Lung Disease stage 0 through 4 (P, 0.001). On multivariable analysis, the Peak Index was significantly associated with CT emphysema (adjusted b = 0.906; 95% confidence interval [CI], 0.789 to 1.023; P, 0.001) and small airways disease (adjusted b = 1.367; 95% CI, 1.188 to 1.545; P, 0.001), St. George’s Respiratory Questionnaire score (adjusted b = 1.075; 95% CI, 0.807 to 1.342; P, 0.001), 6-minute-walk distance (adjusted b = 21.993; 95% CI, 23.481 to 20.506; P, 0.001), and FEV1 change over time (adjusted b = 21.604; 95% CI, 22.691 to 20.516; P = 0.004), after adjustment for age, sex, race, body mass index, current smoking status, pack-years of smoking, and FEV1. The Peak Index was also associated with the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and mortality (P, 0.001). Conclusions: The Peak Index is a spirometry metric that is associated with CT measures of lung disease, respiratory morbidity, lung function decline, and mortality.