Restricted and repetitive behaviors (RRB) are common in individuals with 22q11.2 microdeletion syndrome (22q11.2DS), yet the underlying mechanisms of these behaviors remain poorly characterized. In the present pilot investigation, we aimed to further our understanding of RRB in 22q11.2DS by exploring their relationship with cognitive control and anxiety as well as with sex, chronological age, and full-scale IQ. Parents of 38 children with 22q11.2DS (17 females; Mage = 11.15 years, SD = 2.46) completed the Social Communication Questionnaire as a measure of RRB and social and communication (SC) problems and the Behavioral Assessment System for Children-2 as a measure of anxiety and cognitive control. Higher RRB scores were significantly associated with higher anxiety levels (r = 0.44, P = 0.006), more impairments in cognitive control (r = 0.56, P < 0.001), and higher SC scores (r = 0.43, P = 0.011). In the first step of the hierarchical regression model, anxiety accounted for 24.5% of variance (F = 10.05, P = 0.003); cognitive control accounted for an additional 18.1% of variance (Fchange = 11.15, P < 0.001) in the second step; SC score accounted for only 0.8% of additional variance in the third step (Fchange = 0.40, P = 0.53). The final model explained 43.4% of variance (F = 7.42, P = 0.001), with cognitive control as a unique independent predictor of RRB score (t = 2.52, P = 0.01). The current study provides the first exploration of the cognitive control-anxiety-RRB link in individuals with 22q11.2DS and points to cognitive control as a potentially viable target for treatments aimed at reducing RRB. Autism Res 2019, 12: 1737-1744. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with 22q11.2 deletion syndrome show high levels of repetitive behaviors, however, the previous research has not explored why people with this syndrome exhibit high rates of repetitive behaviors. Understanding the reasons for the high levels of repetitive behaviors is important given that these behaviors can be highly impairing. Our study found that repetitive behaviors were associated with impaired ability to self-regulate and high levels of anxiety. These findings need to be further replicated; however, they are important as they suggest potentially promising ways of reducing these behaviors.