Two-dimensional hydrodynamic simulations were performed on a monthly basis along 2.5 km of the Kvichak River near Igiugig in southwest Alaska, USA, to estimate flow conditions and to assess the hydrokinetic potential of the river reach. Instantaneous power density function along the computational domain was calculated. Study results indicate that two areas may be suitable for deploying turbines. The best option is located near the town, where the channel is relatively straight. A second possible site is located near the end of the study reach (approximately 2.3 km, along the river, from Lake Illiamna). Monthly-averaged velocities along the thalweg ranged from 1.7 to 2.7 m/s; and from 1.1 to 2 m/s at the upstream and downstream sites, respectively. Similarly, averaged values for the instantaneous power density, reduced by an extraction coefficient, were approximately 1500 and 5500 W/m2 during April and September, respectively, at the upstream site, as well as 400 and 2500 W/m2 for the same months at the downstream site. It was found that a previous resource assessment, which considered cross-sectionally averaged velocities, substantially underestimated the available power density along the river reach. Finally, the importance of having adequate bathymetric data is demonstrated by comparing field measurements with model simulations.