Introduction: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR1) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR1 predicts acute exacerbations (AECOPD). Methods: Hundred one COPD patients (FEV1 (SD) 53 (19) % predicted) were prospectively recruited in a multi-center study. HRR1 after the 6MWT was evaluated as the difference between heart rate at the end of the test and 1 min into the recovery (HRR1). Linear and logistic regression was used to identify predictors of HRR1 and AECOPD, respectively. The best HRR1 cut-off point to predict AECOPD was selected using the receiver operating characteristics (ROC) curves. The follow-up period was 12 months. Results: Distance covered during the 6MWT (m) and DLco (% predicted) were independently associated with HRR1 (r2 = 0.51, p = 0.001). Among several potential covariates, HRR1 emerged as the most significant predictor of AECOPD (Odds ratio [OR], 0.91 per beat of recovery; 95% confidence interval [CI], 0.85–0.97; p = 0.02). The ROC analysis indicated that subjects with HRR1 less than 14 beats (AUC, 0.71 [CI] 0.60–0.80; p = 0.0001) were more likely to suffer an exacerbation during the follow-up period (for HRR1, p = 0.004 [log-rank test]). Conclusions: HRR1 after the 6MWT is an independent predictor factor for AECOPD. Further studies are warranted to examine the physiological mechanisms associating a delayed HRR and acute exacerbations in COPD patients.