Bycatch in fishing gear is one of the most pressing conservation issues facing marine mammals today. In the United States a formal regime to address bycatch of marine mammals was adopted in 1994 as Amendments to the Marine Mammal Protection Act (MMPA). This regime provides quantitative conservation goals and a transparent reporting system, allowing for a unique opportunity to assess the efficacy of bycatch mitigation within U.S. waters. In the present analysis, we compile bycatch estimates for each stock of U.S. marine mammals since 1994 to determine whether mitigation efforts under the Amendments have been successful in reducing bycatch. Bycatch trends were analysed on a national level, and for two regional case studies; harbor porpoises in the Gulf of Maine and common dolphins along the U.S. Pacific coast. The estimated annual marine mammal bycatch was 4356 (SE 424) and bycatch levels declined since the MMPA was amended. Harbor porpoise bycatch in the Gulf of Maine was, however, correlated with landings of cod, suggesting that effort controls in the fishery, rather than porpoise conservation measures, were responsible for initial bycatch reduction. Bycatch mitigation efforts were more successful in the Pacific, where higher levels of compliance with mitigation measures are known to occur. We conclude that the 1994 Amendments have in general been successful, but that implementation has not always translated into conservation success, as illustrated by the harbor porpoise case study. Further studies are required to determine factors that promote compliance and mitigation success within the MMPA framework.