OBJECTIVES: To examine profiles of infant regulatory behaviors and associated family characteristics in a community sample of 12-month-old infants and mental health difficulties at 5 and 11 years of age.METHODS: Items relating to demographic characteristics, maternal distress, and infant regulation were completed by 1759 mothers when their infants were 8 to 12 months old. The Strengths and Difficulties Questionnaire was completed by mothers at child ages 5 (n = 1002) and 11 (n = 871) years.RESULTS: Analyses revealed 5 profiles ranging from the most settled infants (36.8%) to those with mainly sleep problems (25.4%), isolated mild-to-moderate tantrums (21.3%), complex regulatory difficulties (13.2%), and complex and severe regulatory difficulties (3.4%). Compared with those in the settled profile, children in the moderately unsettled profile were more likely to score in the clinical range for total difficulties at 11 years of age (odds ratio [OR] 2.85; 95% confidence interval [CI]: 1.28 to 6.36; P , .01), and children in the severely unsettled profile were more likely to score in the clinical range at 5 (OR 9.35; 95% CI: 2.49 to 35.11; P , .01) and 11 years of age (OR 10.37; 95% CI: 3.74 to 28.70; P , .01).CONCLUSIONS: Infants with multiple moderate-to-severe regulatory problems experience substantially heightened odds of clinically significant mental health concerns during childhood, and these symptoms appear to worsen over time. Clinicians must inquire about the extent, complexity, and severity of infant regulatory problems to identify those in the most urgent need of intervention and support.Dr Cook conceptualized the design of the study, drafted the manuscript, analyzed and interpreted the results, and reviewed and revised the manuscript; Drs Giallo and Mensah conceptualized the design of the study, assisted with the data analysis and interpretation of the results, and reviewed and revised the manuscript; Dr Hiscock and Ms Sanchez conceptualized the design of the study, assisted with the interpretation of the results, and reviewed and revised the manuscript; Dr Reilly conceptualized the design of the study, supervised data collection, assisted with the interpretation of the results, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.