A 50-year-old human immunodeficiency virus positive patient who was diagnosed with Pneumocystis jirovecii pneumonia developed severe subcutaneous and mediastinal emphysema, which was progressive despite low pressure mechanical ventilation. Infraclavicular skin incisions and vacuum-assisted closure therapy were used to resolve the emphysema. The subcutaneous emphysema decreased significantly, and after 1 week the vacuum-assisted closure therapy was ended successfully. This technique has previously been described in several case reports, where it is a promising treatment in severe subcutaneous emphysema, but it is not yet widely used. This case report supports the further use of vacuum-assisted closure therapy in subcutaneous emphysema. Successful treatment of severe mediastinal and subcutaneous emphysema in Pneumocystis jirovecii pneumonia can be achieved by vacuum-assisted closure therapy on infraclavicular skin incisions.