Fatigue cracks are an ongoing problem for aluminum high-speed vessels, and preventing fatigue cracks caused by wave loading is expected to be a significant challenge for future aluminum high-speed ferries and military vessels. To aid in this effort, a hot-spot fatigue design approach using first-order reliability methods (FORM) is constructed. Two different limit state functions are investigated, and the accuracy and consistency of the FORM method for the highly nonlinear fatigue limit state equations are evaluated through a comparison with Monte Carlo simulation results. The sensitivity of the resulting safety index to changes in the input variables, and their uncertainties, are presented graphically. The method is compared to existing design standards for four simple structural details.