Transdermal scopolamine is commonly used by mariners to prevent or treat seasickness. Most studies indicate that scopolamine administered transdermally via an adhesive patch does not impair performance of skills required to navigate a vessel, but trials have not been conducted testing navigation and ship handling under realistic conditions. The aim of this study was to test the effects of transdermal scopolamine on performance using training simulators to assess complex vessel navigation and rough-weather ship handling abilities. A randomized double-blind crossover study assessed 32 Swedish maritime cadets under transdermal scopolamine and placebo conditions on simulated navigation and ship handling performance, sleepiness, and subjective measures of fitness and performance. There were no significant differences on occupational outcomes by medication condition, but sustained reaction time was significantly increased under transdermal scopolamine, relative to placebo. We conclude that the transdermal scopolamine patch does not impair simulated ship handling.