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Conservation biologists routinely face the dilemma of keeping small, fragmented populations isolated, wherein inbreeding depression may ensue, or mixing such populations, which may exacerbate population declines via outbreeding depression. The joint evaluation of inbreeding and outbreeding risks in the wild cannot be readily conducted in endangered species, so a suggested ‘safe’ strategy is to mix ecologically and genetically similar populations. To evaluate this strategy, we carried out a reciprocal transplant experiment involving three neighboring populations of endangered Atlantic salmon (Salmo salar) now bred in captivity and maintained in captive and wild environments. Pure, inbred, and outbred (first and second generation) cross types were released and recaptured in the wild to simultaneously test for local adaptation, inbreeding depression, and outbreeding depression. We found little evidence of inbreeding depression after one generation of inbreeding and little evidence of either heterosis or outbreeding depression via genetic incompatibilities after one or two generations of outbreeding. A trend for outbreeding depression via the loss of local adaptation was documented in one of three populations. The effects of inbreeding were not significantly different from the effects of outbreeding. Hence, at the geographic scale evaluated (34–50 km), inbreeding for one generation and outbreeding over two generations may have similar effects on the persistence of small populations. The results further suggested that outbreeding outcomes may be highly variable or unpredictable at small genetic distances. Our work highlights the necessity of evaluating the relative costs of inbreeding and outbreeding in the conservation and management of endangered species on a case-by-case basis.