Polymer-based coagulants, such as amphiphilic polyelectrolytes, are used for water treatment in two distinct ways, as coagulant aids and as primary coagulants. In the latter role, polymers have a number of advantages over inorganic coagulants, notably the smaller volume of sludge produced and reduced sludge management costs. This study examines the impact of molecular structure of novel amphiphilic polyelectrolytes on floc size and size distribution determined by dynamic light scattering. These parameters are related to hydrophobe contents and charge of the polyelectrolyte. These characteristics are also related to the removal efficiency of natural organic matter (NOM). It is expected that a much lower amount of polymer is sufficient when amphiphilic polyelectrolytes are used as primary coagulants/flocculants in treating waters contaminated with NOM. The smaller polymer amount may result in lesser treatment costs as well as yielding a much lower sludge volume. Dynamic light scattering and UV absorbance results confirmed an optimum polymer dose of 0.3 ppm with up to 5% hydrophobe contents. The polymer hydrophobe contents were directly related to the system performance and NOM removal efficiency. The pH of the solution was virtually unaffected.