A case-control study used data in the National Animal Poison Control Center database to characterize risk factors for gastrointestinal ulceration and acute renal failure subsequent to the acute ingestion of ibuprofen in the dog. For gastrointestinal ulceration (GIU) subsequent to ibuprofen ingestion, four factors differentiated the 116 cases from the 93 controls. Risk of GIU was lower for dogs where the time from ingestion to intervention was known as opposed to missing (adjusted odds ratio (aOR) = 0.12, p = 0.0001). Risk of GIU was also lower for the Labrador breed (aOR = 0.22, p = 0.004). Risk of GIU was higher for each unit of the logarithm of time to intervention (aOR = 2.63, p = 0.0002) and for the German Shepherd breed (aOR = 5.67, p = 0.14). For acute renal failure (ARF) subsequent to ibuprofen ingestion, two factors differentiated the 80 cases from the 64 controls. Risk of ARF was lower for dogs where the time from ingestion to intervention was known as opposed to missing (aOR = 0.15, p = 0.0001). Risk of ARF was higher for each unit of the logarithm of time to intervention (aOR = 2.16, p = 0.01). Although this study failed to describe a dose-response relationship, it appears that there are significant breed differences in susceptibility to GIU subsequent to ibuprofen exposure. Time to intervention was critical for both GIU and ARF outcomes. Dogs, particularly German Shepherds, ingesting even small amounts of ibuprofen, may need to be managed aggressively.