A patient with severe chickenpox was admitted to a negative-pressure isolation room. He remained sedated, intubated and mechanically ventilated throughout his admission. He was managed only by nurses immune to chickenpox. A non-immune male nurse occasionally handed equipment through the doorway, without entering the room. Ten days later, he also developed chickenpox. Sequencing of viruses from the patient and nurse showed the same rare genotype, indicating nosocomial transmission. An experimental model demonstrated that, despite negative pressure, opening the door could have resulted in transport of infectious air out of the isolation room, leading to a breakdown in isolation conditions.