The objective of the study was to evaluate the performance of the International Study of Asthma and Allergies in Childhood (ISAAC) video questionnaire in terms of repeatability and accuracy against a clinical diagnosis of asthma achieved according to the National Heart, Lung and Blood Institute (NHLBI) algorithm. Two hundred and forty-one subjects, aged 13-14 years from two secondary schools in Rome, Italy, were enrolled. Video and written ISAAC questionnaires were completed twice, 3 months apart, by 194 and 190 adolescents, respectively. Two months later, 106 subjects were visited by two physicians blinded to the results of questionnaires. Sixteen subjects were classified as having clinical asthma (CA) at the clinical visit, and eight of them as having clinical active asthma (CAA) on the basis of at least one positive outcome of the NHLBI algorithm. The repeatability of video questionnaire was similar to that of the written questionnaire for items on exercise wheeze and nocturnal cough and, to a lesser degree, for items concerning any wheeze in the past. The video questionnaire showed a worse performance than the written questionnaire for items on asthma attack: K-value (95% CL) = 0.59 (0.37-0.80) for video scene no. 5 and K-value (95% CL) = 0.86 (0.74-0.98) for written question no. 6. The overall accuracy of the video questionnaire, estimated as a positive answer to any video scene, was lower in terms of sensitivity than that of any written question when CA was used as a gold standard (0.50 vs. 0.81, P=0.025) and increased with respect to CAA (0.75 vs. 0.87, P = 0.317). The specificity of any video scene was better than that of any written question, independently from the gold standard used. In conclusion, the video questionnaire showed a fairly good accuracy, although slightly lower than that of the written questionnaire and provided sufficiently reliable results. However, samples of subjects from different geographic areas and cultures should be studied in order to conclusively define the performance of the ISAAC video questionnaire.