Background: Around the world, the timing of referral of chronic obstructive pulmonary disease (COPD) patients for pulmonary rehabilitation differs from immediately after exacerbation (early) to later on when patients are in a stable state (late). There are no trials comparing the different time points of referral for pulmonary rehabilitation. Objectives: Our aim was to compare the effects of early and late pulmonary rehabilitation on exacerbation rates and health-related quality of life (HRQOL) in COPD patients with exacerbations. Methods: We randomized COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages II-IV) with a recent exacerbation to early (within 2 weeks) or late pulmonary rehabilitation (starting 6 months after randomization and in a stable state). The primary outcome was the exacerbation rate over 18 months, and secondary outcomes included HRQOL and mortality. We used multivariate analyses and an intention-to-treat analysis approach. Results: We randomized 36 patients to pulmonary rehabilitation. On average, patients with early rehabilitation (n = 19) had 2.61 (SD 2.96) exacerbations requiring systemic corticosteroids and/or antibiotics, compared to 2.77 (SD 3.41) in patients with late rehabilitation (adjusted incidence rate ratio 0.83, 95% confidence interval 0.43-1.63; p = 0.60). Over the 18-month period, patients with late rehabilitation experienced more dyspnea (difference on Chronic Respiratory Questionnaire dyspnea domain 0.74 and on the Medical Research Council dyspnea scale 0.37), but neither these differences nor any difference in HRQOL domains reached statistical significance. Conclusions: We did not find any statistically significant differences between early and late pulmonary rehabilitation. However, our trial indicates that early rehabilitation may lead to faster recovery of HRQOL after exacerbations compared to rehabilitation later on when patients are in a stable state.