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Abstract Background Obesity is one of the major determinants of blood pressure. This study aimed to determine the optimal sex- and age-specific cut-off points of anthropometric indices, including body mass index (BMI), waist circumference (WC), hip circumference (HC), wrist circumference (WrC), waist-hip ratio (WHR), and waist-height ratio (WHtR), to screen for hypertension (HTN) in a cohort of Iranian adults aged 35 to 70 years, and to compare the predictive performance of the indices based on receiver operating characteristic (ROC) curves. Methods This population-based study was carried out on the participants aged 35 to 70 years of the Bandare-Kong Non-Communicable Diseases (BKNCD) Cohort Study, a part of the Prospective Epidemiological Research Studies in IrAN (PERSIAN). Using the area under the receiver operating characteristic curve (AUC) and Youden's J index, optimal sex- and age-specific cut-off points of the anthropometric indices in association with HTN were calculated. Results This study included a total of 2256 females and 1722 males. HTN was diagnosed in 736 females (32.6%) and 544 males (31.6%). The optimal cut-off of WC for HTN was 90 cm in males and 95 cm in females, with an area under the ROC curve (AUROC) of 0.60 and 0.64, respectively. For HC, the optimal cut-off was 95 cm for males and 108 cm for females (AUROC = 0.54 for both). Moreover, WrC optimal cut-offs were 17 cm for males (AUROC = 0.56) and 15 cm for females (AUROC = 0.57). As for BMI, the optimal cut-off was 25 kg/m2 in males and 27 kg/m2 in females (AUROC of 0.59 and 0.60, respectively). Also, a cut-off of 0.92 was optimal for WHR in males (AUROC = 0.64) and 0.96 in females (AUROC = 0.67). On the other hand, WHtR optimal cut-offs were 0.52 for males and 0.60 for females (AUROC of 0.63 and 0.65, respectively). Conclusions WHR and WHtR, as anthropometric indices of obesity, were demonstrated to be significant predictors of HTN. Further, we suggest using WHR (cut-off point of 0.92 for males and 0.96 for females) and WHtR (cut-off point of 0.52 for males and 0.60 for females) as measures of preference to predict HTN among the southern Iranian population. Further multicenter longitudinal studies are recommended for a more accurate prediction of HTN.