The objective of this study was to assess the impact of smoking on health-related quality of life, Work Productivity and Activity Impairment (WPAI) in chronic obstructive pulmonary disease (COPD) patients. Respondents of the 2009/2010 US National Health and Wellness Survey (NHWS), aged ≥ 40 years, with COPD, chronic bronchitis or emphysema, were included in the study. Current and former (had not smoked for ≥ 11 years) smokers were compared. Physical component summary (PCS) and mental component summary (MCS) scores from the Short Form-12 version 2 (SF-12v2), health utilities (SF-6D) and WPAI were evaluated. Differences between current (n = 1685) and former (n = 1932) smokers were revealed: MCS (44.80, 46.73; p < 0.01); PCS (35.12, 35.79; p < 0.1); SF-6D (0.63, 0.65; p < 0.05). WPAI: presenteeism (23%, 18%; p < 0.05); work impairment (25%, 21%; p < 0.05); activity impairment (52%, 49%; p < 0.01). In conclusion, COPD patients who smoke have poorer health-related quality of life, impaired productivity and higher healthcare costs than former smokers.