Objectives . To evaluate the impact of volatile anesthetic choice on clinically relevant outcomes of patients undergoing cardiac surgery. Methods . Major databases were systematically searched for randomized controlled trials (RCTs) comparing volatile anesthetics (isoflurane versus sevoflurane) in cardiac surgery. Study-level characteristics, intraoperative events, and postoperative outcomes were extracted from the articles. Results . Sixteen RCTs involving 961 patients were included in this meta-analysis. There were no significant differences between both anesthetics in terms of intensive care unit length of stay (SMD −0.07, 95% CI −0.38 to 0.24, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.66</mml:mn></mml:math>), hospital length of stay (SMD 0.06, 95% CI −0.33 to 0.45, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.76</mml:mn></mml:math>), time to extubation (SMD 0.29, 95% CI −0.08 to 0.65, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.12</mml:mn></mml:math>), S100<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mrow><mml:mi>β</mml:mi></mml:mrow></mml:math> (at the end of surgery: SMD 0.08, 95% CI −0.33 to 0.49, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.71</mml:mn></mml:math>; 24 hours after surgery: SMD 0.21, 95% CI −0.23 to 0.65, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.34</mml:mn></mml:math>), or troponin (at the end of surgery: SMD −1.13, 95% CI −2.39 to 0.13, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.08</mml:mn></mml:math>; 24 hours after surgery: SMD 0.74, 95% CI −0.15 to 1.62, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.10</mml:mn></mml:math>). CK-MB was shown to be significantly increased when using isoflurane instead of sevoflurane (SMD 2.16, 95% CI 0.57 to 3.74, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn fontstyle="italic">0.008</mml:mn></mml:math>). Conclusions . The volatile anesthetic choice has no significant impact on postoperative outcomes of patients undergoing cardiac surgery.