Objective: This study investigates whether the combination of thiazides with an aldosterone antagonist can decrease their negative effects on the fibrinolytic activity. Methods: Twenty-eight hypertensive patients (20 men, 8 women) visiting our hypertension unit were included in the study. The control group consisted of age- and gender-matched 9 normotensive healthy individuals. The patients in the 1st group (7 men, 2 women, mean age 48.55±6.14 years) were given 50 mg hydrochlorothiazide (HCT), whereas patients in the 2nd group (7 men, 2 women, mean age 48±6.3 years) received a combination of 50 mg HCT and 5 mg amyloride and the 3rd group (7 men, 3 women, mean age 48.2±7.25 years) took 50 mg HCT and 50 mg spironolactone for a period of 2 weeks. The plasminogen activator inhibitor (PAI)-I, tissue plasminogen activator (t- PA) and PAI-I/t-PA ratio were assessed before and after treatment. Results: Treatment with HCT-spironolactone caused an increase in PAI-I (p<0.001) and t-PA ( p<0.001), while no changes were observed in PAI-I/t-PA (P>0.05). In patients treated with HCT-spironolactone, PAI-I increase rate was lower than in those treated with HCT and HCT- amyloride (p<0.001). Hydrochlorothiazide, HCT-amyloride and HCT-spironolactone treatments caused a significant decrease in the base- line blood pressure values (p<0.001). Uric acid levels had increased after treatment with HCT (p<0.01) and HCT-amyloride (p<0.001), but no changes were observed in individuals receiving HCT-spironolactone (p>0.05). Conclusion: Thiazides have a negative effect on the endogenous fibrinolytic activity, which is already impaired in the hypertensive patients. Their use in combination with an aldosterone antagonist such as spironolactone can decrease their hypofibrinolytic effects and metabolic side effects.