Lung perfusion scintigraphy is employed to evaluate patients with severe emphysema who are candidates for lung volume reduction surgery (LVRS). Our purpose was to investigate the role of scintigraphy in relation to chest computed tomography (CT) and lung function in this setting. Six observers blinded to clinical data retrospectively scored preoperative scintigrams of 70 patients undergoing bilateral video-assisted LVRS according to the distribution of lung perfusion as homogeneous, intermediately heterogeneous, or markedly heterogeneous. Heterogeneity of emphysema distribution was also assessed by chest CT. Dyspnea and pulmonary function were measured preoperatively and 3 mo postoperatively. In 42 patients with markedly heterogeneous, in 18 with intermediately heterogeneous, and in 10 with homogeneous perfusion, mean (+/- SE) FEV1 increased by 57 +/- 8% (p < 0.0001), 38 +/- 9% (p < 0.001), and 23 +/- 9% (p = NS) (p = NS for intergroup comparisons). In a multiple regression analysis, functional improvement after LVRS was more closely correlated with preoperative hyperinflation and the degree of emphysema heterogeneity estimated by chest CT than with the degree of perfusion heterogeneity assessed by scintigraphy. In 16 of 22 patients with homogeneous emphysema distribution in the chest CT scintigraphy revealed intermediately or markedly heterogeneous perfusion. We conclude that lung perfusion scintigraphy has a limited role in prediction of outcome, but it may help to identify target areas for resection in LVRS candidates with homogeneous CT morphology.