Use of thrombolytic therapy in pulmonary embolism is restricted in cases of massive embolism. It achieves faster lysis of the thrombus than the conventional heparin therapy thus reducing the morbidity and mortality associated with PE. The compartment syndrome is a well-documented, potentially lethal complication of thrombolytic therapy and known to occur in the limbs involved for vascular lines or venepunctures. The compartment syndrome in a conscious and well-oriented patient is mainly diagnosed on clinical ground with its classical signs and symptoms like disproportionate pain, tense swollen limb and pain on passive stretch. However these findings may not be appropriately assessed in an unconscious patient and therefore the clinicians should have high index of suspicion in a patient with an acutely swollen tense limb. In such scenarios a prompt orthopaedic opinion should be considered. In this report, we present a case of acute compartment syndrome of the right forearm in a 78 years old male patient following repeated attempts to secure an arterial line for initiating the thrombolytic therapy for the management of massive pulmonary embolism. The patient underwent urgent surgical decompression of the forearm compartments and thus managed to save his limb.