Objective This meta-analysis sought to determine whether minimally invasive mitral valve surgery (mini-MVS) improves clinical outcomes and resource utilization compared with conventional open mitral valve surgery (conv-MVS) in patients undergoing mitral valve repair or replacement. Methods A comprehensive search of MEDLINE, Cochrane Library, EMBASE, CTSnet, and databases of abstracts was undertaken to identify all randomized and nonrandomized studies up to March 2010 of mini-MVS through thoracotomy versus conv-MVS through median sternotomy for mitral valve repair or replacement. Outcomes of interest included death, stroke, myocardial infarction, aortic dissection, need for reintervention, and any other reported clinically relevant outcomes or indicator of resource utilization. Relative risk and weighted mean differences and their 95% confidence intervals were analyzed as appropriate using the random effects model. Heterogeneity was measured using the I2 statistic. Results Thirty-five studies met the inclusion criteria (two randomized controlled trials and 33 nonrandomized studies). The mortality rate after mini-MVS versus conv-MVS was similar at 30 days (1.2% vs 1.5%), 1 year (0.9% vs 1.3%), 3 years (0.5% vs 0.5%), and 9 years (0% vs 3.7%). A number of clinical outcomes were significantly improved with mini-MVS versus conv-MVS including atrial fibrillation (18% vs 22%), chest tube drainage (578 vs 871 mL), transfusions, sternal infection (0.04% vs 0.27%), time to return to normal activity, and patient scar satisfaction. However, the 30-day risk of stroke (2.1% vs 1.2%), aortic dissection/injury (0.2% vs 0%), groin infection (2% vs 0%), and phrenic nerve palsy (3% vs 0%) were significantly increased for mini-MVS versus conv-MVS. Other clinical outcomes were similar between groups. Cross-clamp time, cardiopulmonary bypass time, and procedure time were significantly increased with mini-MVS; however, ventilation time and length of stay in intensive care unit and hospital were reduced. Conclusions Current evidence suggests that mini-MVS maybe associated with decreased bleeding, blood product transfusion, atrial fibrillation, sternal wound infection, scar dissatisfaction, ventilation time, intensive care unit stay, hospital length of stay, and reduced time to return to normal activity, without detected adverse impact on long-term need for valvular reintervention and survival beyond 1 year. However, these potential benefits for mini-MVS may come with an increased risk of stroke, aortic dissection or aortic injury, phrenic nerve palsy, groin infections/complications, and increased cross-clamp, cardiopulmonary bypass, and procedure time. Available evidence is largely limited to retrospective comparisons of small cohorts comparing mini-MVS versus conv-MVS that provide only short-term outcomes. Given these limitations, randomized controlled trials with adequate power and duration of follow-up to measure clinically relevant outcomes are recommended to determine the balance of benefits and risks.