Hatchery-reared salmon smolt used for supplementary stocking often display poor migration behavior compared to wild smolt, which reduces the success of this management action. Oxazepam, an anxiolytic drug, has been shown to intensify salmon smolt migration in mesocosm experiments, and treatment with this drug has, therefore, been suggested as a management option to improve downstream smolt migration. In this study, we tested this by assessing migration performance of hatchery-reared Atlantic salmon (Salmo salar) smolt along a 21-km long natural river-to-sea migration route in a boreal river in Northern Sweden. Using acoustic telemetry, the migration rate and survival of smolt that had been exposed to oxazepam (200 μg L-1, N = 20) was monitored and compared with a control group (N = 20) of unexposed smolt. Exposed smolt took significantly longer time to initiate migration after release compared to the control fish, but after that we observed no significant difference in downstream migration speed. However, exposed smolt had considerably higher probability of being predated on compared to control smolt. We attribute these results to increased risk-taking and higher activity in oxazepam-exposed smolt, which in turn increased initial non-directional exploratory behavior and decreased predator vigilance. These results are discussed based on current concerns for ecological implications of behavioral modifications induced by pharmaceutical pollution and climate change. We conclude that exposure to oxazepam is an unsuitable management option to prime migration of reared salmon in natural systems.