Heap leach processing for extraction of gold began in 1985 at Summitville Mine in southwestern Colorado, and by 1994 the site was declared a Superfund Site by the USEPA. In 1995, we began a science-based approach aimed at restoring 200 ha of highly disturbed land. The short-term goal of the restoration was aimed at stabilizing soils and preventing off-site movement of metal-containing sediments. The longer-term goal was to encourage development of a plant community that resembled a reference condition. Here, we describe our systematic approach for restoration that included identification of constraints to plant establishment and growth, a greenhouse experiment to screen 36 growth medium treatments, and a field experiment to test a subset of best performing treatments. A greenhouse study identified several promising treatments that were implemented in the field experiment, which ultimately identified a single best approach (30 cm of waste rock amended with lime and mushroom compost and covered with 15 cm of limed, fertilized stockpiled topsoil). From 1999 to 2001, the site was re-contoured, amended, and seeded. From 2002 to 2009, we documented an increase in uniformity of vegetation cover on restored areas, an increase in species richness, and a significant shift from a plant community dominated by seeded species, to one more similar to a reference plant community as evidenced by a non-metric multi-dimensional scaling analysis. Overall, these results demonstrate how initial well-planned treatments can encourage a favorable trajectory for restoration of a seeded site, while also demonstrating the utility of this science-based approach for dealing with restoration of a highly disturbed landscape.