Marine debris is a widespread and globally recognized problem. Sound information is necessary to understand the extent of the problem and to inform resource managers and policy makers about potential mitigation strategies. Although there are many short-term studies on marine debris, a longer-term perspective and the ability to compare among regions has heretofore been missing in the U.S. Caribbean and the Gulf of Mexico. We used data from a national beach monitoring program to evaluate and compare amounts, composition, and trends of indicator marine debris in the U.S. Caribbean (Puerto Rico and the U.S. Virgin Islands) and the Gulf of Mexico from 1996 to 2003. Indicator items provided a standardized set that all surveys collected; each was assigned a probable source: ocean-based, land-based, or general-source. Probable ocean-based debris was related to activities such as recreational boating/fishing, commercial fishing and activities on oil/gas platforms. Probable land-based debris was related to land-based recreation and sewer systems. General-source debris represented plastic items that can come from either ocean- or land-based sources; these items were plastic bags, strapping bands, and plastic bottles (excluding motor oil containers). Debris loads were similar between the U.S. Caribbean and the western Gulf of Mexico; however, debris composition on U.S. Caribbean beaches was dominated by land-based indicators while the western Gulf of Mexico was dominated by ocean-based indicators. Beaches along the eastern Gulf of Mexico had the lowest counts of debris; composition was dominated by land-based indicators, similar to that found for the U.S. Caribbean. Debris loads on beaches in the Gulf of Mexico are likely affected by Gulf circulation patterns, reducing loads in the eastern Gulf and increasing loads in the western Gulf. Over the seven years of monitoring, we found a large linear decrease in total indicator debris, as well as all source categories, for the U.S. Caribbean. Lower magnitude decreases were seen in indicator debris along the eastern Gulf of Mexico. In contrast, only land-based indicators declined in the western Gulf of Mexico; total, ocean-based and general-source indicators remained unchanged. Decreases in land-based indicators were not related to human population in the coastal regions; human population increased in all regions over the time of the study. Significant monthly patterns for indicator debris were found only in the Gulf of Mexico; counts were highest during May through September, with peaks occurring in July. Inclement weather conditions before the time of the survey also accounted for some of the variation in the western Gulf of Mexico; fewer items were found when there were heavy seas or cold fronts in the weeks prior to the survey, while tropical storms (including hurricanes) increased the amount of debris. With the development around the globe of long-term monitoring programs using standardized methodology, there is the potential to help management at individual sites, as well as generate larger-scale perspectives (from regional to global) to inform decision makers. Incorporating mechanisms producing debris into marine debris programs would be a fruitful area for future research.