A comprehensive methodology to assess the hydrokinetic potential of a reach of the Tanana river near Nenana, Alaska, is developed to help determine the suitability of the reach for installing and operating hydrokinetic electric turbines. The methodology utilizes field measurements and two-dimensional model simulations to define the discharge, velocity, power density, turbulence, and Froude number throughout the river reach. Thalweg stability is assessed using the maximum cross-sectional velocity, specific discharge, and turbulence. The thalweg was determined to be stable, for the current river condition, from the upstream end of the reach to about 800 m downstream. From 800 m to the end of the reach, at 1100 m, river hydrodynamics indicate an unstable thalweg shifting towards the right bank. The thalweg instability is associated with the transition between upstream and downstream river bends, which may migrate with river stage, bed load, existing bed conditions, and other factors. The flow is subcritical with an average Froude number of 0.30 along the thalweg. Averaged measured velocities along the thalweg are about 1.5 m/s. The average value for instantaneous power density is approximately 4500 W/m2 at the period of measurement (late August). Study results indicate that hydraulic conditions in the river reach may be suitable for turbine operations above the 800 m location with the exception of a possible eddy located around the 400 m location.