Information about predictors of decline in pulmonary function (forced expiratory volume in 1 second [FEV1]) or health-related quality of life (HRQoL) in patients with asthma or (chronic obstructive pulmonary disease [COPD]) might help to determine those who need additional care. A 2-year prospective cohort study was conducted among 380 asthma and 120 COPD patients. In both asthma and COPD patients, a 2-year change in FEV1 was only weakly associated with a 2-year change in HRQoL (r = .0.19 and 0.24, respectively). In both groups, older age, living in an urban environment, and a lower peak expiratory flow rate (PEFR) at baseline were associated with a decline in FEV1. Additional predictors of FEV1 decline were greater body weight, less chronic cough or sputum production, and less respiratory symptoms in asthma patients and current smoking in COPD patients. A decline in HRQoL was associated with older age, non-compliance with medication, more dyspnea, and a lower PEFR in asthma patients and with male gender, lower education, lower body weight, more dyspnea, and more respiratory symptoms in COPD patients. Our results show that FEV1 and HRQoL appear to represent different disease aspects influenced by different predictors.