While there were no high-level prospective randomized controlled trials, 8 were lower-quality randomized controlled trial, 3 were retrospective cohort studies, and 4 were case series. Most studies pooled results of facial and nonfacial cutaneous applications. Three studies focused solely on oculofacial applications, and these were all lower-level evidence studies. The study outcomes included scar dimension reduction, erythema, patient satisfaction score, observer assessment of scar improvement, and recurrence rates. 5-Fluorouracil was administered as monotherapy or as part of multimodality treatment with other agents (usually corticosteroids) or with CO2 laser, radiotherapy, or pulsed dye laser. 5-Fluorouracil was usually given as an intralesional injection, but in some studies, it was applied topically after micropuncture of the skin. The number and timing of treatments varied between studies. Overall, the level of safety of 5-FU was high. Pain with injection was the most common reported side effect. Other common adverse side effects included pruritus, telangiectasias, changes in pigmentation, and purpura, and 2 studies noted more serious events, such as ulceration, superficial necrosis, and local infection. There were no severe side effects such as anaphylaxis, immune suppression, secondary malignancy, systemic infection, blindness, or death. In all studies, 5-FU was associated with prophylaxis of oculofacial scars or improvement of keloids or hypertrophic scars in terms of reducing size, erythema, and pruritus. 5-Fluorouracil application was associated with favorable patient satisfaction and observer assessment scores especially compared with corticosteroid injections alone.