• A change from baseline in: WHO functional class, SF-36 health survey, Borg dyspnea index, B-type natriuretic peptide (BNP) [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
• Monotherapy treatment status [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
• Failure-free treatment status [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
• Long-term survival [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
• Worsening of pulmonary hypertension. [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]

• Secondary endpoints will include:
• Clinical worsening of pulmonary hypertension
• A change from baseline in: WHO functional class, SF-36 health survey, Borg dyspnea index, B-type natriuretic peptide (BNP)
• Monotherapy treatment status
• Failure-free treatment status
• Long-term survival

The primary objective of this study is to evaluate the safety and efficacy of ambrisentan in a broad population of subjects with pulmonary hypertension. Secondary objectives of this study are to evaluate the effects of ambrisentan on other clinical measures of PAH, long-term treatment success, and survival.

This study will enroll up to 200 subjects with PAH and in PH subgroups including PH associated with interstitial lung disease (ILD); PH due to chronic thromboembolic disease or sickle cell disease; PH associated with chronic obstructive pulmonary disease (COPD); PAH associated with congenital heart defects; and PAH associated with HIV. Subjects may be receiving prostacyclin or sildenafil therapy at baseline, and subjects who previously discontinued either bosentan, sitaxsentan, or both, due to liver function test abnormalities are eligible.

Summarized Inclusion Criteria:

1. 18 years of age or older
2. Current diagnosis of PH associated with an acceptable etiology as outlined in the protocol, including: IPAH, FPAH, PH associated with ILD, PH due to chronic thromboembolic disease or sickle cell disease, PH associated with COPD, and APAH secondary to the scleroderma spectrum of disease, systemic lupus, erythematosus, anorexigen use, congenital heart defects, or HIV infection
3. Stable regimen (within four weeks) of chronic prostanoid, PDE-5 inhibitor, calcium channel blocker, or HMG-CoA reductase inhibitor therapy
4. Right heart catheterization completed prior to screening must meet pre-specified criteria
5. Female subjects of childbearing potential must have a negative serum pregnancy test and must agree to use a reliable double method of contraception until study completion and for at least four weeks following their final study visit.
6. Male subjects must be informed of the potential risks of testicular tubular atrophy and infertility associated with taking ambrisentan and queried regarding his understanding of the potential risks as described in the Informed Consent Form.

Summarized Exclusion Criteria:

1. Participation in a previous clinical study with ambrisentan
2. Bosentan or sitaxsentan use within four weeks prior to the screening visit
3. AST or ALT lab value that is greater than 1.5 times the upper limit of normal at the screening visit
4. Pulmonary function tests not meeting pre-specified criteria
5. Contraindication to treatment with ERA

5. History of malignancies other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the past five years 6. Female subject who is pregnant or breastfeeding