Heart failure (HF) is a complex disease and a major cause of morbidity and mortality worldwide. Natriuretic peptides (NPs) are involved in the pathogenesis of HF, but their activity may be modified by polymorphisms in the genes encoding them. Aim: To examine the associations of NPPA:rs5065 and NPPB:rs198389 polymorphisms with the risk of HF and cardiovascular phenotypes in Polish patients with HF. The study group comprised 330 HF patients, and the control group comprised 206 healthy newborns. Genomic DNA was extracted from blood, and genotyping of both polymorphisms was performed using polymerase chain reaction–restriction fragment length polymorphism. There were no significant differences in the distributions of NPPA and NPPB genotypes between HF patients and controls. Within the HF group, there were no significant associations between the frequencies of type 2 diabetes, hypertension, left ventricular hypertrophy, or categories of left ventricular ejection fraction (LVEF) and the NPPA or NPPB variants. However, LVEF was significantly higher in NPPA CC homozygotes than in carriers of at least one T allele. The results of our study did not confirm an association between the NPPA:rs5065 or NPPB:rs198389 polymorphisms and predisposition to HF or HF intermediate phenotypes, except for LVEF.