No-take marine reserves or no-take zones (NTZ) have become an effective tool for restoring marine populations threatened by overfishing by allowing populations to recover from excessive extraction and eventually export larvae and/or adults to adjacent areas (spillover). In 2004, a NTZ was established within the Mona Island Natural Reserve, Puerto Ricos largest and most distant marine protected area (MPA). Mona Island is important as a potential stepping stone across a partial biogeographic barrier, yet populations there are thought to be largely dependent upon selfrecruitment. Thus, it is critical that the effectiveness of this NTZ be evaluated. The objective of this study is to evaluate the effectiveness of the Mona Island NTZ with respect to coral reef fish populations threatened by overfishing. We used a before-after-control-impact (BACI) design to analyze these effects. Fish abundance and biomass of selected species known to be fishery targets were used as indicators of NTZ effect. Belt transects and roving surveys, stratified by habitat type and depth, were used to quantify fish abundances and sizes in areas previously sampled in 2005/06 (before reserve effects would be evident). Permutational multivariate analyses of variance (PERMANOVA) were carried out to assess temporal changes between 2005/06 and 2009/10, and spatial differences between take and NTZ of Mona Island. Significant increases in fish abundance and biomass were observed, suggesting a NTZ effect for important fishery resources. This study provides information to determine if marine reserve goals are being achieved at this bio-geographically important Caribbean site.