Objective. To evaluate the impact on the outcome of some invasive and non-invasive parameters in patients with unoperated Eisenmenger syndrome (ES) before starting specific treatment for PAH. Methods. Patients, before starting specific therapy, underwent basal. At follow-up, we considered clinical worsening. Results. 29 consecutive patients (12M, 17F, age 36.8±12.5) were followed-up for 33.1±11 months. All were treated with oral bosentan. 10 patients (group A) had clinical worsening and 19 (group B) did not. At basal clinical evaluation there was no significant difference between group A and B (WHO class 3.4±0.5 vs 3.1±0.4, p=ns). At 6MWD test group A and B were not significantly different in walking distance (310±128 vs 293±106m, p=ns) and O2 saturation at the end of the test (75±6 vs 73±8%, p=ns; O2 saturation reduction -11±2 vs -14±4%; p=ns). At right heart catheterization there was no significant difference in QP/QS (0.7±0.2 vs 0.9±0.5), indexed cardiac output (2.9±1.1 vs 3.2±1.2 l/min/m2, p=ns), indexed pulmonary vascular resistances (iPVR: 19±7 vs 23±15 WU/m2; p=ns), mean pulmonary arterial pressure (72±18 vs 79±14 mmHg; p=ns). At vasoreactivity test, Group A (poorer prognosis) showed a significantly lower reduction of iPVR (-41±13% vs -62±18%, p<0.01). A reduction <50% of iPVR had a sensitivity of 80% and a specificity of 79% for poorer prognosis at a long term follow-up. Only 1/29 showed a positive response to the vasoreactivity test according to guidelines criteria. Conclusions. A reduction of iPVR <50% at vasoreactivity test is associated with a poorer prognosis in Eisenmenger syndrome at a long term follow-up.