The purpose of this study was to identify risk factors and initial symptoms of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). From the CARPIS (Case Reports of Adverse Drug Reactions and Poisoning Information System) database, which contains 35,000 case reports of adverse drug reactions (ADRs), we selected 101 cases (case group) matching the criteria for TEN/SJS provided by the Japanese Ministry of Health, Labour and Welfare. We also selected 590 controls (control group) who had also taken the drugs suspected of causing TEN/SJS in the case group. Various data were compared between the case group and the control group and analyzed statistically. A comparison between the case group and the control group based on logistic regression analysis yielded 2 factors that were associated with a significant elevation of TEN/SJS risk : infectious diseases (OR=1.84, 95% CI=1.18-2.86) and collagen disease (OR=2.58, 95% CI=1.14-5.44). In addition, age (OR=0.38, 95% CI=0.15-0.94) and history of allergy or ADRs (OR=0.48, 95% CI=0.25-0.87) were associated with a significant reduction in the risk. Based on logistic regression analysis of the initial symptoms, itching (OR=0.17, 95% CI=0.07-0.34) was associated with a significant reduction in the risk of TEN/SJS, and sore throat (OR=3.15, 95% CI=1.44-6.60) with a significant elevation of the risk. The present study thus uncovered some risk factors for TEN/SJS that would be helpful in preventing severe drug reactions.