Secale cereale is a serious weed problem in winter Triticum aestivum–producing regions. The interference relationships and economic thresholds of S. cereale in winter T. aestivum in Colorado, Kansas, Nebraska, and Wyoming were determined over 4 yr. Winter T. aestivum density was held constant at recommended planting densities for each site. Target S. cereale densities were 0, 5, 10, 25, 50, or 100 plants m−2. Secale cereale–winter T. aestivum interference relationships across locations and years were determined using a negative hyperbolic yield loss function. Two parameters—I, which represents the percent yield loss as S. cereale density approaches zero, and A, the maximum percent yield loss as S. cereale density increases—were estimated for each data set using nonlinear regression. Parameter I was more stable among years within locations than among locations within years, whereas maximum percentage yield loss was more stable across locations and years. Environmental conditions appeared to have a role in the stability of these relationships. Parameter estimates for I and A were incorporated into a second model to determine economic thresholds. On average, threshold values were between 4 and 5 S. cereale plants m−2; however, the large variation in these threshold values signifies considerable risk in making economic weed management decisions based upon these values.