BACKGROUND: The significance of early membrane exposure on the regenerative outcome in guided tissue regeneration (GTR) and guided bone regeneration (GBR) procedures is somewhat controversial. Several clinical trials have shown better response when the membranes remained submerged (S) compared to those that have become exposed (E) during healing. Other studies have failed to show any such difference. Small sample size and/or large standard deviation of the changes might account for these discrepancies. The purpose of this meta-analysis is to critically combine the existing data in order to provide meaningful information based on a large database. METHODS: Studies of GTR in Class II furcation and intrabony defects (IBD), together with GBR around dental implants, where the membrane became exposed during the postoperative period, were combined to form 3 separate databases. A meta-analysis was employed to compare the 2 subgroups (E versus S) in each of the databases. First, weighted mean changes and weighted standard errors were calculated for each subgroup. Next, an individual study P value was calculated (1-tailed Student t test); finally, a combined Fisher's P statistic (with 5% significance level) was calculated from the individual P values. RESULTS: Five studies with a total of 101 sites were included in the furcation database; 43 of these sites became exposed. Mean horizontal attachment level (AL) gain for the S sites (3.72 +/- 0.15 mm) was slightly greater than that of the E sites (3.06 +/- 0.15 mm; P = 0.030257). For the intrabony group, there were 309 sites in 5 studies: of these, 142 sites became exposed. Mean gain in vertical AL was 4.22 +/- 0.15 mm and 4.69 +/- 0.13 mm for the E and S group, respectively (P = 0.011415). The GBR group included 60 sites in 2 studies: new bone formation in the 24 S sites (3.01 +/- 0.38 mm) was 6-fold greater compared with the 36 E sites (0.56 +/- 0.45 mm). These differences were also statistically significant (P = 0.001875). CONCLUSIONS: Membrane exposure during healing had a major negative effect on GBR around dental implants but only a minimal effect on GTR around natural teeth.