Background: Utilization of intra-aortic balloon pump (IABP) and left ventricular assist device (LVAD) during percutaneous coronary intervention (PCI) has increased in recent years. We analyzed the trends and predictors of hospitalization cost associated with high risk PCI in US over a 5 year period (2005-2010). Methods: We queried the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (NIS) between 2005 and 2010 using the ICD9 procedure code of 36.07 and 36.06 for PCI. The NIS represents 20% of all hospitals in the US and is the largest all payer hospital discharge database. We defined high risk PCI as PCI plus LVAD (ICD-9 code 37.68, 37.62) or IABP placement (ICD-9 code 37.61) during the same hospital admission. We examined the selective contribution of patient demographics, insurance type, and hospital characteristics, Deyo modification of Charlson comorbidity index (CCI) and hospital PCI volume (split into quartiles with first quartile as referent) to hospitalization cost. For each year, cost was adjusted for inflation according to the 2010 cost. The independent predictors of hospitalization cost were calculated by mixed effects linear regression modeling incorporating hospital ID as random effects. Results: 26,300 (weighted n = 130,151) number of patients were identified. Overall hospitalization cost associated with high risk PCI increased from $137,354 in 2005 to $160,736 in 2010 (P<0.001), with $131,239 in 2005 to $158,937 in 2010 for IABP (P<0.001) and $185,774 in 2005 to $243,657 in 2010 for LVAD (P<0.001). The independent predictors of increased hospitalization cost associated with high risk PCI on a multivariable analysis included teaching hospital (+$10,212, p = 0.005), CCI = 2 (+$17,824, p= 0.001), CCI 3 or more (+$36,354, p= 0.001), presence of myocardial infarction (MI) or shock (+$9,094, p<0.001) and occurrence of any of periprocedural complication (+$68,704, p<0.001). The independent predictors of decreased hospitalization cost for high risk PCI included use of IABP vs. LVAD (-$51,783, p<0.001), female sex (-$3,567, p =0.01) and private insurance (-$6,840, p=0.001) or self-pay, no insurance (-$10,541, p<0.001) compared to Medicare/Medicaid as referent. Conclusion: In this observational study we demonstrated that increased hospitalization cost for high risk PCI is associated with teaching hospital, CCI, presence of MI or shock and occurrence of periprocedural complications. We also found use of IABP, female sex, having private, self-pay or no insurance to be associated with a decreased hospitalization cost related to high risk PCI in the US over a 5 year period from 2005-2010.