Anaphylaxis is a rarely reported yet potentially fatal adverse effect of apixaban. This case involves a patient in her 60s who presented with left leg swelling and was diagnosed with bilateral deep vein thrombosis. Less than an hour after ingestion of therapeutically indicated apixaban, she experienced dyspnoea, hypoxia, hypotension and an urticarial rash. She was promptly treated with epinephrine, diphenhydramine and methylprednisolone and found to have an elevated tryptase level, a reliable marker for anaphylactic reactions. She clinically improved, transitioned to enoxaparin and was discharged the following day. This case encourages healthcare providers to consider anaphylaxis as a rare but potentially lethal side effect of apixaban.