Background: Major risk factors of hypertension (HTN) including obesity, insulin resistance, renal pathology, increased sympathetic nerve activity (SNA) and vascular inflammation are associated with hyperleptinemia. Therefore hyperleptinemia may act as a mediator of blood pressure, linking body fat mass with changes in insulin action, sympathetic neuronal outflow and renal pathology. Objective: The objective of our study was to explore the relationship between hyperleptinemia and HTN in Pakistani population. Materials and Methods: It was a case control study of 6 months duration, carried out at Shifa College of Medicine and Shifa International Hospital, Islamabad. One hundred and four male subjects, 52 with HTN and 52 without HTN were included in this study. Leptin levels were measured by enzyme-linked immunosorbent assay (ELISA) technique. The relationship of leptin (LEP), body mass index (BMI), fasting blood sugar (FBS) and cholesterol levels with blood pressure were assessed. Results: Patients with HTN versus patients without HTN had a higher body mass index (28.0 +/- 0.12 to 24.11 +/- 0.27 kg/m(2)), FBS (169.20 +/- 7.34 to 127.50 +/- 2.30 mg/dl), total cholesterol (160 +/- 3.72 to 158 +/- 2.71 mg/dl) and LEP (53.40 +/- 5.32 to 21.65 +/- 3.50 ng/ml) levels. In univariate analysis, obesity, hyperglycemia and hyperleptinemia (with P values of 0.000, 0.001, 0.000, respectively), whereas in multivariate analysis, hyperglycemia and hyperleptinemia (with P values of 0.006 and 0.001, respectively) were risk factors for HTN. Our study also showed that hyperleptinemia is an independent risk factor for HTN. Conclusions: We observed a strong positive relationship between hyperleptinemia and hypertension, thereby indicating that increased leptin levels could be considered as a risk factor for HTN and cardiovascular disease. Further studies are needed to probe the underlying pathophysiological mechanisms responsible for hyperleptinemia in HTN.