Disease and aging-related factors may predispose chronic obstructive pulmonary disease (COPD) patients to impaired balance, although the underlying determinants of impaired balance in COPD patients are still unknown. The purpose of this study was to identify the determinants of impaired balance in COPD patients. Also, we aimed to determine which balance measures (clinical or laboratory tests) are more indicative in determining balance impairment in these patients. This cross-sectional study recruited 24 patients with moderate to severe COPD and 24 age-matched healthy subjects. Participants were evaluated regarding demographic and clinical data, previous falls history, lower limb muscle strength, exercise capacity, physical activity and balance level. COPD patients exhibited significantly alonger test duration on timed up and go test, ahigher sway index on the postural stability and lower directional control score on the limit of stability of Biodex balance system (all, p < 0.001) compared to healthy controls, whereas there was no difference in Berg balance scale score between groups (p > 0.05). Balance impairment of the patient group was significantly associated with nonpulmonary conditions, such as physical activity level, exercise capacity, lower limb muscle strength, and with fall history. Also, COPD patients represented significantly lower physical activity level and exercise capacity, weaker lower limb muscle strength than healthy controls (all, p < 0.001). Patients with moderate to severe COPD exhibit apparently important reductions in balance control that is directly associated with nonpulmonary consequences and fall history. These results may be extremely important to fall prevention and to guide the development of interventions for this population.