Outcomes of patients undergoing cavopulmonary palliation for single ventricle physiology may be impacted by living at altitude, as the passive pulmonary circulation is dependent on the resistance of the pulmonary vascular bed. The objective of this study is to identify risk factors for failure of cavopulmonary palliation at elevated altitude. Between January 1995 and March 2007, 122 consecutive patients living at a mean altitude of 1600 m (range 305 to 2570) underwent a bidirectional Glenn (BDG). There was one in-hospital mortality and 7 late deaths. 52 have proceeded to the Fontan procedure. Survival after BDG was 92.4% at 5 years. Freedom from palliation failure, defined as death, transplant, BDG/Fontan takedown, or revision was 81% at 5 years. At a mean follow-up of 39.8 months, 90 patients (75%) were in New York Heart Association class I. Patients with failing cavopulmonary circulation had higher pre-BDG pulmonary artery pressure (PAP) (18.3+/-6.1 mm Hg versus 14.8+/-5.1 mm Hg, P=0.016) and higher pre-BDG transpulmonary gradient (TPG) (11.2+/-6.2 mm Hg versus 7.7+/-4.3 mm Hg, P=0.014). Post-BDG, patients with palliation failure had increased PAP (15.0+/-5.7 mm Hg versus 10.8+/-2.8 mm Hg, P=0.008) and indexed pulmonary vascular resistance (PVRI) (2.43+/-1.0 Wood U . m(2) versus 1.52+/-0.9 Wood U . m(2), P=0.007). The majority of patients at moderate altitude have favorable outcomes after BDG or Fontan palliation. Risk factors for palliation failure at elevated altitude include PAP >15 mm Hg, TPG >8 mm Hg, and PVRI >2.5 Wood U . m(2).