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This study examines differences in score profiles on the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) for transgender and gender-diverse (TGD) youth in a clinical setting. Data were collected from youth receiving services at a gender care clinic in the Midwestern United States. Inclusion criteria were youth that identify as transgender, nonbinary, or another gender-diverse identity label between the ages of 6 and 18 and received services between October 2017 and November 2021. The analytic sample (N = 177) included 51.4% transmasculine, 17.5% transfeminine, 22.6% nonbinary/gender-expansive, and 8.5% questioning youth. 88.1% of youth were White. Wilcoxon signed-rank tests compared differences in mean T scores when using male versus female scoring templates for YSR and CBCL separately. Statistically significant differences were found on the majority of scales, particularly for TGD adolescents. For example, significant differences were found on the YSR for 10 of 11 scales for transmasculine and transfeminine youth ages 11–18 and 9 of 11 scales for nonbinary/gender-expansive youth. McNemar's test revealed significant differences in the number of clinical range scores for transmasculine YSR respondents on Anxious/Depressed, Somatic Complaints, Thought Problems, and Internalizing scales. For CBCL comparison of clinical significance, significant differences were found for Anxious/Depressed, Attention Problems, and Total Problems scales for transmasculine youth ages 12–18. Selecting a scoring template is contextually relevant; however, template selection appears to matter less when examining clinical relevance. Results suggest that clinicians using the CBCL and YSR with TGD youth have flexibility in scoring template selection. Public Significance Statement: When using screening measures with transgender and gender-diverse (TGD) youth to assess for mental health challenges that only have binary (male or female) scoring templates, like the Child Behavior Checklist and Youth Self-Report, scoring template selection does impact scores but does not result in large clinical differences. Clinicians using these screeners with TGD youth have flexibility on which scoring template to use, including scoring with both templates. [ABSTRACT FROM AUTHOR]