BACKGROUND: Cleft lip and palate patients undergo a significant number of interventions during their childhood and adolescence. Although the intention of such interventions is to improve psychosocial functioning, there exists a paucity of data on the psychosocial outcomes of the burden of care on cleft children. In this work, the long-term effects of quantity and timing of childhood operations on teenagers with cleft lip and palate were evaluated. METHODS: Cleft lip and palate patients (aged 14 to 17 years; n = 55) and an age-matched unaffected cohort (n = 14) prospectively enrolled from two institutions were administered the anger, anxiety, and depressive symptoms instruments from the Pediatric Patient-Reported Outcomes Measurement Information System. Total number of operations and operations stratified by age groups (0 to 7, 8 to 10, 11 to 13, and 14 to 17 years) were evaluated in relationship to instrument scores. Descriptive statistics, independent t tests, Pearson correlations, and multiple linear regression analyses were conducted. RESULTS: No differences in overall psychosocial functioning were found between the cleft lip and palate and comparison groups. Total quantity of childhood operations did not correlate to psychosocial functioning of cleft lip and palate teenagers. However, multiple linear regression analyses demonstrated that increased number of operations in the 8- to 10-year-old age range predicted increased anxiety and depressive symptoms in teenagers (β = 0.38, p = 0.009; and β = 0.29, p = 0.03, respectively). CONCLUSIONS: It was previously reported by the authors group that the 8- to 10-year-old age range is an at-risk period for psychosocial distress in children with craniofacial anomalies. Their current work demonstrates that increased number of operations during this time frame may result in long-term consequences in anxiety and depression in cleft lip and palate patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.