Objective: Pulmonary hypertension (PHT) is associated with high mortality and morbidity. Interest has increased in the use of drugs that, because of their neurohumoral inhibitory effects, inhibit the renin angiotensin system. In this study, we sought to examine whether losartan therapy is non-inferior to nifedipine in the treatment of secondary PHT. Methods: This prospective randomized study consisted of 63 patients (mean age, 63.7±9.1 years) with PHT who underwent Doppler echocardiographic examination. A baseline 6-minute walk test (6MWT) and cardiopulmonary exercise test (CPET) were performed, and the endothelin-1 level of each patient was measured. Patients were assigned to two groups receiving treatment with nifedipine (n=30) and losartan (n=33). After 2 months of treatment, those measurements were repeated. The groups were compared with regard to effectiveness for the studied parameters using 2*2 factorial ANOVA design for repeated measurements. Results: When posttreatment values were compared with baseline values in both groups, the following statistically significant changes were noted: the mean values of both mean and systolic pulmonary artery pressures (PAPs) were reduced (p<0.05) on Doppler echocardiography; exercise duration, work rate, and end-tidal carbon dioxide pressure (PETCO2) were higher (p<0.05 for all); and the minute ventilation (VE) and ventilatory equivalents for carbon dioxide (VE/VCO2) were lower (p<0.05 for both) according to the results of a CPET. No statistically significant change was noted in the mean levels of serum endothelin-1. With regard to the results cited above, no statistically significant difference was detected between the losartan and nifedipine groups (p > 0.05). Conclusion: The findings of this study indicate that losartan is non-inferior to nifedipine for reducing PAP and improving exercise capacity. However, the short-term use of losartan or nifedipine had no statistically significant effect on endothelin-1 levels in patients with secondary PHT.