Disruption of usual routines may hinder adherence, increasing the risk of rejection. We aimed to compare weekend versus weekday medication adherence among adolescent and young adult kidney transplant recipients, hypothesizing poorer adherence on weekends. We examined data from the Teen Adherence in Kidney transplant Effectiveness of Intervention Trial (TAKE-IT). We assessed the 3-month run-in period (no intervention) and the 12-month intervention interval, considering a potential interaction between weekend/weekday and treatment group. Adherence was monitored using electronic pillboxes in participants 11-24 years followed in eight transplant centers in Canada and the United States. We used logistic regression with generalized estimating equations to estimate the association between weekends/weekdays and each of perfect taking (100% of prescribed doses taken) and timing (100% of prescribed doses taken on time) adherence. Taking (OR = 0.72 [95% CI 0.65-0.79]) and timing (OR = 0.66 [95% CI 0.59-0.74]) adherence were poorer on weekends than weekdays in the run-in (136 participants) and the intervention interval (taking OR = 0.74 [0.67-0.81] and timing OR = 0.71 [95% CI 0.65-0.77]). There was no interaction by treatment group (64 intervention and 74 control participants). Weekends represent a disruption of regular routines, posing a threat to adherence. Patients and families should be encouraged to develop strategies to maintain adherence when routines are disrupted. TAKE-IT registration number: Clinicaltrials.gov registration: NCT01356277 (May 17, 2011). © 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.