Synthetic inputs have become the norm in cash grain production in the Midwest U.S., but do they really increase profitability compared with low-input production methods? This study reports a comparison of cash grain yields, quality and profitability under two management systems, low-input practices and conventional practices. The crop sequence was corn, soybean, and wheat - medium red clover green manure. Low-input practices included crop rotation, manure, and mechanical weed control. Conventional practices added starter fertilizer, side-dress N for corn, early spring topdress N for wheat and herbicides to the low-input practices. The conventional inputs increased yields in each of the five growing seasons, 1992–96. Weather, N fertilizer and weed control appeared to explain much of the yield and grain quality variation. Soil P and K levels were maintained or increased by manure use. Plant foliar analysis indicated that soil macronutrients were mostly in the sufficient range for both management systems. Economic return in excess of the additional cost of the fertilizer and herbicides averaged $172.63 ha−1 for soybean, $165.63 ha−1 for corn and minus $19.19 ha−1 for wheat over the five-year study. Fertilizer and herbicides did pay with corn and soybean, but not with wheat under the conditions of this study.