With rising input costs and environmental concerns, growers are seeking methods to minimize nitrogen (N) inputs and off-field N losses while maintaining crop yields. Field studies on processing butternut squash (Cucurbita moschata Duchesne ex Poir.) were conducted in 2004–2007 at 11 locations in Ontario, Canada, to determine the optimal N rate and estimate potential N losses. Preplant broadcast ammonium nitrate was applied at five rates between 0 and 220 kg N/ha. In contrasting years (i.e., cool/wet versus warm/dry versus average), 64% of sites were nonresponsive to N fertilizer as indicated by no differences in marketable squash yield. In responsive sites, the most economical rate of N (MERN) was between 105 and 129 kg N/ha of N fertilizer, indicating that the Ontario-recommended rate of 110 kg N/ha seems appropriate for responsive sites. At 110 kg N/ha, no yield advantage resulted from using a controlled-release N (CRN) or split-applying ammonium nitrate at preplant and vine elongation at 65 + 45 kg N/ha, respectively, compared with the same amount applied preplant. Apparent N losses (N inputs – N outputs) at harvest were 83 and 29 kg N/ha greater at a fertilizer application rate of 220 kg N/ha than at 0 and 110 kg N/ha, respectively. At 110 kg N/ha, crop removal balance and apparent N loss calculations suggest relatively low risk of N loss from the field during the growing season and after harvest, respectively. However, environmental and economical risks would be minimized if nonresponsive sites could be identified before N fertilizer application.