With limited herbicide options and a growing concern to herbicide-resistant weeds, there is a strong need for additional chemical weed control materials in tobacco. S-metolachlor is labeled for use in a variety of agronomic and horticultural crops in the United States, and for use in tobacco internationally. S-metolachlor has been shown to be effective in providing residual weed control of common weed species in tobacco production, such as yellow nutsedge (Cyperus esculentus), Palmer amaranth (Amaranthus palmeri), and various annual grasses. The objectives of this research are to, i) evaluate tobacco tolerance to S-metolachlor at different rates (1,069 g ai/ha and 2,138 g ai/ha) and application methods (pre-transplant incorporated (PTI) and pre-transplant (PRE-T), ii) evaluate crop and weed response to herbicide programs currently recommended by Cooperative Extension, and iii) to generate efficacy and pesticide residue data that will support a federal label for U.S. tobacco production. Visual estimates of percent weed control and crop injury were recorded at two, six, and nine weeks after transplanting. Cured leaf yield, quality, and value were also documented. At one location, severe stunting and plant death was observed with PTI applications, regardless of application rate (50-75 % of non-treated check). Stunting was minimal (<10 %) in all PRE-T treatments across all locations. Treatments comprised of S-metolachlor and other herbicides resulted in better weed suppression than treatments with S-metolachlor alone. Preliminary results indicate that S-metolachlor may be a suitable candidate for use in tobacco production when applied PRE-T or post-directed after transplanting.