Previous research has established the role of resistance training (RT) on muscle function in adolescents, but a lack of evidence to optimize RT for enhancing muscle quality (MQ) exists. This study examined whether RT frequency is associated with MQ in a nationally representative adolescent cohort. A total of 605 adolescents (12−15 year) in NHANES were stratified based on RT frequency. MQ was calculated as combined handgrip strength divided by arm lean mass (via dual-energy X-ray absorptiometry). Analysis of covariance was adjusted for sex, race/ethnicity, and arm fat percentage; p < 0.05 was considered significant. RT frequency was associated with MQ for 2−7 day/week but not 1 day/week. When no RT was compared to 1−2 and 3−7 day/week, associations were present for 3−7 day/week but not 1−2 day/week. When comparing no RT to 1−4 and 5−7 day/week, associations existed for 5−7 day/week but not 1−4 day/week. Next, no RT was compared to 1, 2−3, and 4−7 day/week; associations were found for 4−7 day/week, while 2−3 day/week had a borderline association (p = 0.06); there were no associations for 1 day/week. Finally, no RT was compared to 1, 2, 3, 4, and 5−7 day/week; associations were present for all except 1 and 3 day/week. These prospective data suggest a minimum RT frequency of 2 day/week is associated with MQ in adolescents as indicated by the lack of differences in MQ between 1 day/week RT versus no RT.