Purpose: To evaluate the indications and outcomes of amniotic membrane transplantation (AMT) performed within the first 2 weeks of presentation in the management of patients with acute Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Methods: A retrospective chart review from January 1998 to May 2011 identified 128 SJS/TEN patients admitted to Loyola University Medical Center Burn intensive care unit. The degree of initial ocular surface inflammation was graded as mild, moderate, or severe within the first 2 weeks of admission. Patients were managed either medically or with amniotic membrane (AM). Outcomes were graded as good [best-corrected visual acuity (BCVA) >20/40], fair (BCVA 20/40 to 20/200 or with ocular surface discomfort, requiring contact lens or reconstructive surgeries), or poor (BCVA <20/200). Results: Of the 182 eyes (91 patients) with documented inpatient eye examinations, 108 eyes (59.4%) had mild or no initial ocular involvement, 37 eyes (20.3%) had moderate, and 37 eyes (20.3%) had severe inflammation. Of the 29 patients (58 eyes) with greater than 1 month of follow-up, 17 patients (33 eyes) were treated with medical management and 13 patients (25 eyes) were treated with early AM. One of the 23 eyes with moderate or severe presentation treated with early AMT (4.3%) resulted in a poor outcome within 3 months compared with 8 of 23 eyes (34.8%) that were medically managed (P = 0.022). Conclusions: We present the first case–control study of the use of AM in the management of acute SJS/TEN. Early use of AMT prevents severe vision loss in SJS/TEN patients with initial moderate or severe ocular surface inflammation.