Objective: Identification of young children who are likely to have multi-trigger wheezing is very important for early diagnosis and treatment of asthma. We investigate an index for predicting multi-trigger wheezing in infants with first episode of wheezing. Methods: One-hundred twenty-eight infants (2-20 months) with first episode of wheezing were followed for two years. Personal and family history of atopic diseases was recorded. Wheezing severity was evaluated using the Preschool Respiratory Assessment Measure. Sputum samples were collected from patients, stained with hematoxylin and eosin and studied by optical microscopy. The largest Creola body in sputum was located and the number of shed exfoliated airway epithelial cells (EAECs) counted. Recurrent wheezing was observed and classified as multi-trigger wheezing or non-multi-trigger wheezing. The predictive value of EAECs, family or personal history of atopic disease and the severity of wheezing for subsequent development of multi-trigger wheezing was analyzed. Results: Better predictive performance was achieved by considering the three measures together than by considering each separately. Receiver operator characteristic analysis showed that an index combining wheezing severity score of 9495 sputum EAECs and a family or personal history of atopic disease had a sensitivity of 95.1%, specificity of 74.2%, a positive predictive value of 58.6% and a negative predictive value of 93.6% for prediction of multi-trigger wheezing. Conclusion: For infants with first episode of wheezing, wheezing severity score, family or personal history of atopic disease and number of EAECs in sputum can predict future multi-trigger wheezing.