Background We sought to review the evidence from the available randomized controlled trials (RCTs) regarding the effect of thiazolidinedione therapy on in-stent restenosis after percutaneous coronary intervention. Methods The studies in our meta-analysis were retrieved from search on the PubMed database and from references in relevant articles. Included studies were RCTs that provided comparative data regarding the effectiveness of 6-month pioglitazone or rosiglitazone therapy on the prevention of in-stent restenosis after coronary stent implantation as assessed by quantitative coronary angiography. Results Five RCTs that included 235 evaluable patients who underwent coronary stent implantation and received a 6-month pioglitazone or rosiglitazone therapy were included in our meta-analysis. Restenosis rate was significantly lower in patients who received thiazolidinedione therapy in addition to standard therapy (3 RCTs, 170 patients, odds ratio 0.29, 95% Cl 0. 15-0.56, random effects model). Percentage diameter stenosis was significantly lower in the pioglitozone-rosightazone arm (3 RCTs, 170 patients, weighted difference in means 14.35, 95% Cl 19.99-8.72, random effects model). Minimal lumen diameter of the target lesion was significantly higher in patients who received thiazolidinedione therapy (3 RCTs, 170 patients, weighted difference in means 0.43, 95% Cl 0.21-0.65, random effects model). Patients who received thiazolidinediones were significantly less likely to undergo target lesion revascularization due to restenosis (4 RCTs, 197 patients, odds ratio 0.24, 95% Cl 0.09-0.61, random effects model). Conclusions Our study suggests that thiazolidinedione therapy in patients undergoing coronary stent implantation may be associated with less in-stent restenosis and repeated revascularization. Decisions on clinical use of this therapy must await larger double-blind clinical trials.