Direct oral anticoagulants (DOACs) have gained increasing popularity in clinical practice in the past decade. While DOACs have fewer associated adverse events as compared to warfarin, DOAC-induced hypersensitivity is a rare adverse event that has been reported in the literature. We describe a case of apixaban-induced hemorrhagic pruritic rash in a 62-year-old man with protein C deficiency for which he was receiving warfarin. During hospitalization for another issue, his anticoagulant was converted to apixaban. Within 6 hours of receiving the first dose of apixaban, he developed a hemorrhagic pruritic rash around his buttocks area and extending into his groin. The following day, apixaban was replaced with rivaroxaban, while the rash continued to worsen and spread further around his back. After 3 days of DOAC therapy, the patient was reverted back to warfarin and within 24 hours the rash subsided. This case report indicates a potential rare adverse drug reaction that may become more prominent given the increasing utilization of DOACs in clinical practice. Future research is needed to further investigate this adverse event and ensure that providers and patients are aware of it. Additionally, this report documents to our knowledge, the first report of an immediate hypersensitivity reaction to DOACs.