Objective Medical procedures, particularly venipuncture (the puncture of a vein especially for the withdrawal of blood), can cause serious distress and behavior disturbance for many children. Noncompliance to blood draws can have significant ramifications in both research and clinical settings. The negative reactions may be exacerbated in individuals with autism spectrum disorders (ASD). Even so, there has been little research into the prevalence of the problem or effective intervention procedures. In response to these concerns, we developed and evaluated the Blood Draw Intervention Program (BDIP). The program was designed to be easy to use, require little provider or family time, effectively reduce negative behaviors and increase blood draw compliance. Method In a quasi-randomized trial over the course of approximately 18 months, 58 of 210 families with children with ASD participating in a larger study of phenotypic and genotypic factors reported significant concerns about blood draws and elected to use the BDIP. Results Completion of the program increased blood draw compliance rates from 85.4% to 96.6 % (OR = 4.80, 95% CI = 1.12, 20.59 p = 0.03). Conclusion Results indicate the efficacy of the program in a research setting and suggest a potential clinical application. The current intervention, unlike many others for the same or similar difficulties proposed in the past, was successful without requiring extensive time, training, or effort on the part of providers, parents or their children, nor did it require large scale institutional changes.