Transforming growth factor beta 1 (TGF-β1) is considered a pleotropic cytokine involved in the progression of cardiovascular disease. The purpose of the current study was to identify the relationship between serum levels of TGF-β1, the genetic variations (C509T rs1800469, T869C rs1800470) and their constructed haplotypes with the susceptibility of ischemic heart disease (IHD) in the Iraqi population.The case-control study enrolled 200 participants, including 100 patients with IHD and 100 healthy controls. Genotypes of (TGF-β1) polymorphisms were performed by TaqMan allele-specific probes detected by real-time PCR (RT-PCR). The serum level of TGF-β1 was measured by an ELISA assay. The obtained results showed that the two minor alleles of C509T rs1800469 and T869C rs1800470 were associated with a decreased risk of IHD, preventive fraction (PF%) = 11.6 %; 23.9 %, respectively. Genotype distribution was significantly noted in the TT genotype of C509T rs1800469 (p = 0.033) and in the TC genotype of T869C rs1800470 (p = 0.006) between patients and control groups. A significant distribution was seen in the C allele of T869C rs1800470 (p = 0.002) between the studied groups. The carriers of the TT genotype in the C509T rs1800469 and the TC; CC genotypes in the T869C rs1800470 decreased the chance of having IHD, (hazard ratio HR<1). Furthermore, the haplotype analysis observed that H1 (C-T) was significantly associated with the development of IHD (HR=1.66; 95 % CI=1.10-2.51; p = 0.021) and the inverse effect of H4 (T-C), (HR=0.36; 95 % CI=0.20-0.65; p = 0.001). The TGF-β1 alleles of both SNPs, TT genotype of C509T rs1800469, TC, CC of T869C rs1800470 and H4 locus of haplotypes were suggested to be protective biomarkers against IHD in Iraqi population.