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The role of thrombolysis in pulmonary thromboembolism is controversial. We describe a case of life-threatening acute pulmonary embolism where thrombolysis was successfully administered because of extreme refractory hypoxaemia. We suggest that profound refractory hypoxaemia in this clinical setting was due to the combination of severe right ventricular dysfunction and shunting from pulmonary infarction. The shunt was not likely to have resolved in the short term, but right ventricular function and hypoxaemia improved with clot lysis. Similar clinical presentations should prompt active consideration of thrombolysis.