Objective To compare salivary cortisol baseline levels and responsivity as well as behavioral distress to intravenous (IV) catheter insertions in 4- to 10-year-old children with (n = 29) and without (n = 339) attention-deficit/hyperactivity disorder (ADHD). Methods This is a secondary data analysis from a sample of 542 children who participated in a multisite study on distraction. Data included were demographic variables, Pediatric Behavior Scale-30, Observational Scale of Behavioral Distress-Revised, and four salivary cortisol samples. Results Home samples from the ADHD group revealed nonsignificant but higher cortisol levels than the non-ADHD group. However, on the clinic day, the ADHD group had significantly lower cortisol levels before (0.184 vs. 0.261, p = .040) and 20–30 min after IV insertion (0.186 vs. 0.299, p = .014) compared with the non-ADHD group. Conclusions Cortisol levels in children with and without ADHD differ in response to the stress of an IV insertion.