Background To assess whether age of onset and duration of stimulant therapy for attention‐deficit/hyperactivity disorder (ADHD) are associated with cocaine, methamphetamine, and prescription stimulant misuse during adolescence. Methods Nationally representative samples of US 10th and 12th grade students (N = 150,395) from the Monitoring the Future study were surveyed via self‐administered questionnaires from 16 annual surveys (2005–2020). Results An estimated 8.2% of youth received stimulant therapy for ADHD during their lifetime (n = 10,937). More than one in 10 of all youth reported past‐year prescription stimulant misuse (10.4%)—past‐year cocaine (4.4%) and methamphetamine (2.0%) use were less prevalent. Youth who initiated early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years) did not have significantly increased adjusted odds of cocaine or methamphetamine use relative to population controls (ie, non‐ADHD and unmedicated ADHD youth). Youth who initiated late stimulant therapy for ADHD (≥10 years old) and for short duration (<1 year) had significantly higher odds of past‐year cocaine or prescription stimulant misuse in adolescence than those initiating early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years). Youth who initiated late stimulant therapy for ADHD (≥10 years) for short duration (<1 year) had significantly higher odds of past‐year cocaine, methamphetamine, and prescription stimulant misuse versus population controls during adolescence. No differences in past‐year cocaine, methamphetamine, and prescription stimulant misuse were found between individuals who only used non‐stimulant therapy for ADHD relative to youth who initiated early stimulant therapy (≤9 years old) and for long duration (≥6 years). Conclusions An inverse relationship was found between years of stimulant therapy and illicit and prescription stimulant misuse. Adolescents with later initiation and/or shorter duration of stimulant treatment for ADHD should be monitored for potential illicit and prescription stimulant misuse.