A recent study using the microarray for single-nucleotide polymorphisms (SNPs) genotyping specifically designed for the Japanese population in combination with genome-wide imputation showed the association of several SNPs with cold medicine-related Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with severe ocular complications. However, it remains to be determined whether these polymorphisms are associated with the onset of antipyretic analgesic (AA)-related SJS/TEN, the progression of severe ocular involvements (SOIs), or both AA-related SJS/TEN and SOI phenotypes. To gain a better understanding of the features of these genetic markers, we compared the allele and carrier frequencies of these SNPs among our original SJS/TEN patient groups: (a) AA-related SJS/TEN with SOIs, (b) AA-related SJS/TEN without SOIs, and (c) AA-unrelated SJS/TEN with SOIs. AA-related SJS/TEN with SOIs were found to be associated significantly with both rs6500265 [allele frequency: odds ratio (OR): 2.18; 95% confidence interval (CI): 1.30–3.65; P=0.0052; carrier frequency: OR: 2.52; 95% CI: 1.33–4.78; P=0.058] and rs9933632 (allele frequency: OR: 2.28: 95% CI: 1.37–3.79; P=0.0032; carrier frequency: OR: 2.76; 95% CI: 1.46–5.22; P=0.0031). In contrast, allele and carrier frequencies of these SNPs in patients with AA-related SJS/TEN without SOIs or with SOIs not treated with any AAs were comparable with those in healthy Japanese controls. Collectively, our findings indicate that the rs6500265 and rs9933632 SNPs could be specific markers for AA-related SJS/TEN with SOIs, suggesting that certain genetic backgrounds contribute toward the etiology of this complex syndrome.