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Extubation of ventilated infants with severe unilateral pulmonary interstitial emphysema is difficult because the function of normal lung tissue is impaired. Continued positive pressure ventilation worsens hyperinflation on the side with interstitial emphysema, leading to cardiorespiratory compromise. Resection of affected single lobes is well described, but there are no reported cases of multiple lobectomies in very low birthweight infants. We describe a case where resection of both right upper and middle lobes was successful, allowing extubation within a few days of surgery. Computed tomography (CT) of the chest was helpful in making the decision to treat this infant by surgery.