Introduction: Intravenous fosphenytoin is widely used for acute exacerbation of trigeminal neuralgia, however, few studies have investigated this treatment. We aimed to examine the efficacy and side effects of initial intravenous fosphenytoin plus oral tapering of phenytoin for exacerbation of trigeminal neuralgia. Methods: Consecutive patients with primary trigeminal neuralgia were included in this prospective observational 90-days follow-up study. Data were collected using standardized interviews before, at 24 hours, day 7, 30 and 90 post loading dose. The primary outcome was the proportion of responders defined as a 50% reduction in pain intensity 24 hours post loading dose. Results: We included 15 patients. Nine patients (60%) were responders. Pain intensity 24 hours post loading dose was reduced by 5.00 points on the numerical rating scale (p < 0.001), and at day 7 by 5.5 points (p < 0.001). The most common side effects were hypotension and dizziness. Conclusion: Intravenous fosphenytoin relieves trigeminal neuralgia pain in most patients and provides a window for titrating prophylactic trigeminal neuralgia medications or planning neurosurgery. The decision to administer intravenous fosphenytoin should be taken with support from trigeminal neuralgia experts and involves considerations of co-morbidities and other treatment options for acute exacerbation of trigeminal neuralgia. Clinical Trial: Preregistered (ClinicalTrials.gov Identifier: NCT03712254