For the three-site combinations, the SPARCL1 genotype combinations of rs1049539/rs7695558/rs1049544 (TT/AG/CC: AOR = 0.117; TT/GG/CC: AOR = 0.276; TC/AG/CC: AOR = 0.425), rs1049539/rs1049544/rs1130643 (TT/CC/TC: AOR = 0.149), and rs7695558/rs1049544/rs1130643 (AG/CC/TC: AOR = 0.348) were associated with a reduced risk of ischemic stroke. This evidence concerns the gene SPARCL1 and ischemic stroke.