Nitrification inhibitors are often applied with ammonium containing nitrogen (N) fertilizer or animal manure to increase N-use efficiency and corn (Zea mays L.) yields. However, data are limited specifying when and where applications of nitrification inhibitors are profitable. Growers evaluated economic performance of Instinct (an encapsulated form of nitrapyrin) with fall-applied liquid swine manure in on-farm replicated strip trials in Iowa. Eleven trials with Instinct added to liquid swine manure were conducted in 2009 and 15 trials in 2010. The manure was applied at optimal N rates in at least three strips with and without the inhibitor. The late-season corn stalk nitrate test and digital aerial imagery of the corn canopy were used to assess the post-season corn N status. Yield responses (YR) to the inhibitor were calculated by dividing fields into 30-m long grid cells, and hierarchical analysis was conducted to estimate the probability of economic YR at different field-level factors (rainfall and total N rate) and within-field level factors (soil organic matter and drainage). On average, the inhibitor produced no YR in relatively normal 2009 and a 0.14 Mg ha^-1 YR in extremely wet 2010. The inhibitor did not increase N uptake, but in both treatments about 50% of stalk samples were tested deficient in 2009 and 70% in 2010. In 2010, fields received >25 cm of spring rainfall were about 70% more likely to have economic YR (> 0.12 Mg ha^-1) than fields received <25 cm of spring rainfall. In both years, within-field variability in YR was about five times larger than among-field variability, but within field-level factors had no effects on YR to the inhibitor. The results suggest that the inhibitor may have worked too early to produce economic YR, and its application may be limited to fields often receiving above-normal spring rainfalls.