RATIONALE: This is the first multicenter RCT to evaluate effectiveness and safety of Zephyr® Endobronchial Valve EBV® out to 12-months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation (CV) in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV: Standard-of-Care (SoC)) at 24 sites. Primary outcome at 12-months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of ≥15%. Secondary endpoints included absolute changes in post-BD FEV1, Six-Minute Walk Distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ) scores. RESULTS: 190 subjects, 128 EBV and 62 SoC were randomized. At 12-months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 ≥15% (p