Purpose The aim of this study was to explore the safety and efficacy of bivalirudin in elderly patients undergoing percutaneous coronary intervention (PCI). Methods An electronic search was conducted for randomized controlled trials with outcomes of interest in the elderly (>= 65 years of age). Pooled risk ratios (RR) and 95% confidence interval (CI) using random effects Der Simonian-Laird models were calculated. Primary outcomes were net adverse clinical events (NACE) and major bleeding events at 30 days. Secondary outcomes were major adverse cardiac events (MACE) at 30 days. MACE, all-cause mortality, and NACE at 6-12 months were also examined. Results Eleven trials that randomized a total of 15,895 elderly patients undergoing PCI to bivalirudin versus heparin were included. At 30 days, bivalirudin was associated with a reduced risk of NACE (0.86 [0.75-0.99], p = 0.04), mainly driven by reduction in major bleeding events (0.66 [0.54-0.80], p < 0.0001), as compared with heparin. On subgroup analyses based on the use of GPI in the heparin arm, benefit of major bleeding associated with bivalirudin appeared to be equally evident when GPI was used as a bailout (0.66 [0.46-0.94], p = 0.02) versus routine (0.67 [0.51-0.88], p = 0.004) adjunctive therapy with heparin. Subgroup analyses stratified by clinical presentation showed that benefit of bivalirudin in reducing NACE was even more obvious in the elderly group presenting with ST segment elevation myocardial infarction (STEMI) (0.76 [0.65-0.89], p = 0.0007), as compared with the overall (acute coronary syndrome or stable ischemic heart disease) group. No difference in MACE (0.94 [0.82-1.09], p = 0.42) was demonstrated between the two groups. Bivalirudin was associated with a similar risk of NACE (0.74 [0.39-1.42], p = 0.36) at 6 months and MACE (0.90 [0.68-1.19], p = 0.45) at 6-12 months, while a non-statistically significant trend toward lower all-cause mortality (0.70 [0.47-1.06], p = 0.09) at 1 year. Conclusion In elderly patients undergoing PCI, bivalirudin was associated with a lower risk of major bleeding events and the magnitude of benefit was not related to the use of GPI and irrespective of clinical presentation. Bivalirudin may reduce the NACE, particularly in elderly patients presenting with STEMI or in the setting of routine GPI use in the heparin arm, while no difference in MACE was demonstrated between the two groups.