(1) Background: Between the beginning of the coronavirus pandemic and summer 2022, we distinguished four pandemic waves, with different characteristics of the affected patients. This study investigated the impact of patient characteristics on the outcome of inpatient pulmonary rehabilitation (PR). (2) Methods: Using a prospective approach, the characteristics of post-acute COVID-19 patients of the different waves who participated in inpatient PR were compared based on their assessments and results collected as part of PR (Cumulative Illness Rating Scale (CIRS), six-minute walk test (6-MWT), Pulmonary Function Testing (PFT), and Functional Independent Measurement (FIM). (3) Results: A total of 483 patients were included in the analysis (Wave 1 n = 51, Wave 2 n = 202, Wave 3 n = 84, Wave 4 n = 146). Compared to Wave 3 + 4, patients of Wave 1 + 2 were older (69 vs. 63 years;p< 0.001), had a significantly lower CIRS (13.0 vs. 14.7 points;p= 0.004), had significant better PFT (FVC: 73 vs. 68%pred;p= 0.009; DLCOSB: 58 ± 18 vs. 50 ± 17%pred;p= 0.001), and showed significantly more comorbidities (2.0 vs. 1.6 n/pers.;p= 0.009). Wave 3 + 4 showed significantly greater improvements according to the 6-MWT (147 vs. 188 m;p< 0.001) and the FIM (5.6 vs. 21.1 points;p< 0.001). (4) Conclusions: Patients of the COVID-19 infection waves differed significantly according to their anthropometric data, incidence of comorbidities, and impact of the infection. All cohorts achieved clinically relevant and significant functional improvements during PR, with significant higher improvements in Wave 3 + 4.