Most measures of dyspnea assess a single aspect (intensity or distress) of the symptom. We developed the Multidimensional Dyspnea Profile (MDP) to measure qualities and intensities of the sensory dimension and components of the affective dimension. The MDP is not indexed to a particular activity and can be applied at rest, during exertion, or during clinical care. We report on the development and testing of the MDP in patients with a variety of acute and chronic cardiopulmonary conditions. One hundred fifty-one adults admitted to the ED with breathing symptoms completed the MDP three times in the ED, twice at least 1 h apart (T1, T2), and near discharge from the ED (T3). Measures were repeated in 68 patients twice in a follow-up session 4 to 6 weeks later (T4-T5). The ED sample was 56% men with a mean age of 53 ± 15 years; the follow-up sample was similar. Factor analysis resulted in a two-factor solution with a total explained variance of 63%, 74%, and 72% at T1, T2, and T3, respectively. One domain related to primary sensory qualities and immediate unpleasantness, and the second encompassed emotional response. For the two domains, Cronbach α ranged from 0.82 to 0.95, and the intraclass correlation coefficient ranged from 0.91 to 0.98. Repeated-measures analysis was significant for change (T1, T3, T4), showing responsiveness to change in MDP domains with treatment (F([2,66]) = 19.67, P > .001). These analyses support the reliability, validity, and responsiveness to clinical change of the MDP with two domains in an acute care and follow-up setting.