The Grand Calumet River (GCR), located in northern Indiana, is contaminated due to a wide range of historical industrial activities. This study was conducted to determine the influence of sediment remediation within the GCR on concentrations of chemical contaminants and toxicity to sediment-dwelling organisms. Between 2005 and 2016, sediments with high concentrations of metals and toxic organic compounds were remediated through a combination of removal, addition of activated carbon and organoclay amendments, and capping with sand or relatively uncontaminated sediment. Short-term and long-term sediment toxicity tests with the amphipod Hyalella azteca, the midge Chironomus dilutus, and the mussel Lampsilis siliquoidea were conducted with samples collected in 2013, 2015, and 2017, from 29 sites, including both remediated and non-remediated sites. Sediment chemistry and toxicity data for three groups of remediated sites (US Steel, West Branch, and East Branch) were compared to samples from contaminated but unremediated sites and to relatively uncontaminated reference sites. In general, remediated sediments had lower levels of PAHs, PCBs and metals, although sediments from the US Steel area still had elevated levels of PAH, PCB and chromium. Sediments from the three remediated sites and from reference sites showed significantly reduced toxic effects in short-term sediment bioassays, compared to unremediated sites. Variation in the long-term success of remediation may reflect site-specific factors such as the type of remediation and the potential for recontamination from uncontrolled sources.