To prospectively evaluate the effect of inpatient pulmonary rehabilitation (iPR) on anxiety and depression as outcome measures in patients with COPD, we studied 149 consecutive adults COPD referred to our iPR after an exacerbation. Patients were divided according to the GOLD staging into: Group 1 (stage 2a, n = 48, FEV1 63 +/- 9% pred.), Group 2 (stage 2b, n = 53, FEV1 42 +/- 6% pred.) and Group 3 (stage 3, n = 48, FEV1 25 +/- 7% pred.). The iPR consisted of twelve 3-hours daily sessions. Hospital Anxiety Depression (HAD) Scale as well as 6-minute walk (6MWD) with evaluation of dyspnea (D) and leg fatigue (F) at rest and end of effort, and health related quality of life by means of St. George Respiratory Questionnaire (SGRQ) were assessed before (T0) and after (T1) the iPR. 6MWD, D and F at end of effort and SGRQ total score similarly improved (p < 0.001) in all groups after iPR. The mean level of HAD-anxiety (from 9.1 +/- 4.0 to 7.7 +/- 3.5, from 9.0 +/- 4.6 to 7.2 +/- 4.6 and from 8.1 +/- 4.1 to 6.7 +/- 4.3 in group 1,2 and 3 respectively) and HAD-depression (from 9.4 +/- 3.5 to 8.2 +/- 3.5, from 9.1 +/- 4.2 to 8.2 +/- 4.5 and from 9.0 +/- 4.0 to 7.4 +/- 4.5 respectively) similarly changed (p < 0.0001) over time in all groups. The total percentage of patients with abnormal score (> 10) of HAD-anxiety (from 31% to 21%) and HAD-depression (from 30% to 22%) significantly decreased (p < 0.05) after the iPR. Inpatient pulmonary rehabilitation may improve levels of anxiety and depression as well as symptoms, exercise capacity and health related quality of life in moderate to severe COPD patients after an acute exacerbation.