Government agencies that develop infrastructure such as roads, waterworks, and energy delivery often impact natural ecosystems, but they also have unique opportunities to contribute to the conservation of regional natural resources through compensatory mitigation. Infrastructure development requires a planning, funding, and implementation cycle that can frequently take a decade or longer, but biological mitigation is often planned and implemented late in this process, in a project-by-project piecemeal manner. By adopting early regional mitigation needs assessment and planning for habitat-level impacts from multiple infrastructure projects, agencies could secure time needed to proactively integrate these obligations into regional conservation objectives. Such practice can be financially and ecologically beneficial due to economies of scale, and because earlier mitigation implementation means potentially developable critical parcels may still be available for conservation. Here, we compare the integration of regional conservation designs, termed greenprints, with early multi-project mitigation assessment for two areas in California, USA. The expected spatial extent of habitat impacts and associated mitigation requirements from multiple projects were identified for each area. We used the reserve-selection algorithm MARXAN to identify a regional greenprint for each site and to seek mitigation solutions through parcel acquisition that would contribute to the greenprint, as well as meet agency obligations. The two areas differed in the amount of input data available, the types of conservation objectives identified, and local land-management capacity. They are representative of the range of conditions that conservation practitioners may encounter, so contrasting the two illustrates how regional advanced mitigation can be generalized for use in a wide variety of settings. Environmental organizations can benefit from this approach because it provides a platform for collaboration with infrastructure agencies. Alone, infrastructure agency mitigation obligations will not satisfy all greenprint objectives, but they can be a major contributor to the ongoing process of implementing ecologically sustainable regional plans. © 2009 by the author(s).