Ergotism is a rare but potentially serious condition characterised by peripheral vasospasm. Its diagnosis is challenging because the presentation varies depending on the type and location of the affected blood vessels. Ergot alkaloids, including ergotamine, are metabolised by the cytochrome P450 isoenzyme CYP3A4. Concurrent use of ergotamine with CYP3A4 inhibitors can significantly increase the risk of ergotism. However, this potentially dangerous drug interaction is often underestimated in general practice. Herein, we report the case of a middle- aged woman with a history of migraine headaches, who was treated with Cafergot (ergotamine tartrate and caffeine). After the initiation of human immunodeficiency virus therapy with Kaletra (lopinavir/ritonavir), she experienced recurrent episodes of bluish discoloration, livedo reticularis and tingling sensation in her upper and lower extremities over several years. Despite multiple hospital visits and extensive diagnostic workups, including normal blood investigations and biopsy, the correct diagnosis of ergotism-induced vasospasm due to ritonavir-ergotamine interaction was delayed. This diagnosis was supported by CT angiography, which demonstrated vasospasm of the femoral arteries. The patient's symptoms significantly resolved following ergotamine discontinuation. Ergotism is a self-limiting condition that can be fatal if not recognised and treated promptly. This case highlights the importance of awareness, particularly in primary care settings, on the potential drug interaction, principally in patients receiving drugs that inhibit CYP3A4, such as protease inhibitors. Clinicians should have a low threshold for suspecting ergotism in patients with recurrent or unexplained limb pain, numbness and skin changes, especially if they have a history of ergot alkaloid use.