OBJECTIVE: To evaluate the effects of whole-body resistance training on exercise capacity, health-related quality of life (HRQOL), and muscle strength in patients hospitalized for exacerbation of chronic obstructive pulmonary disease. DESIGN: Randomized controlled trial. SETTING: University hospital. PARTICIPANTS: Patients (N=46) were randomized to either a control group (CG) or training group (TG), and 29 patients completed the study. INTERVENTION: Training consisted of weight-lifting exercises for 6 muscle groups in the upper and lower limbs (2 sets of 8 repetitions each), and the initial load was set at 80% of the 1-repetition maximum load. MAIN OUTCOME MEASURES: Patients were evaluated on the second day of hospitalization, at hospital discharge, and 30 days postdischarge. Patients were evaluated on the basis of the 6-minute walking distance (6MWD), HRQOL, muscle strength, systemic inflammatory markers, and level of physical activity in daily life (PADL). RESULTS: The CG showed a reduction in the strength of lower-limb muscles (P<.05) but not in the 6MWD (P>.05). In contrast, patients from the TG improved strength in the lower-limb muscles and 6MWD during and 30 days after hospitalization (P<.05). The TG also improved the impact domain in HRQOL after hospitalization. No improvement in PADL was observed in the TG. Finally, a reduction in the blood levels of inflammatory markers was observed only in the TG after hospitalization. CONCLUSIONS: Our results suggest that resistance training during hospitalization improves the 6MWD, HRQOL, and lower-limb muscle strength, without altering the levels of systemic inflammation. However, future research should explore this intervention in larger randomized trials.