<b><i>Background:</i></b> Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. <b><i>Objective:</i></b> We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. <b><i>Method:</i></b> Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] &#x3e;55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV₁) and St George’s Respiratory Questionnaire (SGRQ) total score at 6 months. <b><i>Results:</i></b> Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV₁ 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV₁ was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by −10.6 [−15.9 to −5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. <b><i>Conclusion:</i></b> Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.