The prevalence of pain medication use for adolescent knee pain and factors associated with use are not well understood. This study aimed to determine the self-reported use of pain medication for knee pain and identify factors associated with use in adolescents (age 10-19) with longstanding knee symptoms. In this exploratory cross-sectional study, we performed a secondary analysis of data previously collected in 323 adolescents with longstanding knee pain. Factors associated with pain medication use were assessed using multivariable logistic regressions. Analyses were repeated with stratification by age, sex, sport participation frequency, knee pain duration, and knee pain intensity. Among 323 adolescents (mean age 14.4 ± 2.5, 73% female), 84% had patellofemoral pain, (peri- or retro-patellar pain during loaded bending of the knee) and 16% had Osgood-Schlatter Disease (apophysitis with swelling and localized pain at the tibial tuberosity). Twenty-one percent (95% CI 16-25%) of adolescents reported pain medication use for their knee pain, with no difference in usage between those ≤ vs. > 15 years of age (21%, 95% CI 16-27% vs. 20%, 95% CI 13-29%). Adolescents with patellofemoral pain reported greater usage than their counterparts with Osgood-Schlatter Disease (22%, 95% CI 17-28% vs. 12%, 95% CI 4.5-24.3%). The most consistent factor associated with use was knee-related symptoms, observed in both the overall (OR 0.97, 95% CI 0.94-0.99) and stratified analyses (ORs ranged from 0.89 to 0.96). Approximately one in five adolescents with longstanding knee pain reported pain medication use, particularly in adolescents with patellofemoral pain. Knee-related symptoms most consistently associated with the use of pain medications in this population. Future longitudinal studies with data collected at multiple time-points are needed to validate these findings. Self-reported pain medication use is common in adolescents with longstanding knee pain, even though whether pharmacological therapy is the best pain management option at this young age is debatable. Reliance on pain medication at an early age could potentially hamper the development of healthy pain coping strategies and increase the risk of dependence and misuse later in life. Future studies should assess the safety, efficacy, and risks of long-term use of pain medications for adolescent knee pain.