Background. Renal transplant recipients regularly fail to take their prescribed immunosuppressive medications, frequently leading to adverse outcomes. Methods. Medication vials incorporating electronic monitor circuits in their caps compiled prospective data files on the azathioprine dosing patterns of 180 adult renal transplant recipients monitored up to 4 years. These patients were followed for a mean of 8.7 years posttransplantation. Results. Patients were divided into three groups by the medication doses missed during the first 6 months posttransplant. These initial dosing patterns remained remarkably consistent up to 4 years. Patients (n = 47) missing the most doses (≥5%) experienced earlier and more frequent acute rejection episodes (P = 0.025). This group also demonstrated significantly longer interdose intervals (P = 0.005), with more frequent (P<0.001) and longer (P<0.001) "drug holidays." A patient subgroup with early declining medication adherence (n = 23) experienced dramatically poorer outcomes, with significantly increased acute rejection (P < 0.001), chronic rejection (P = 0.034), graft loss before death (P < 0.001), and death (P = 0.04). In all tertiles there was a trend toward missing more medication over time. Conclusions. Excellent posttransplant medication adherence is critical to improved outcomes. Individual dosing patterns are established early after hospital discharge and remain remarkably consistent, despite gradual erosion in adherence over time. The later consequences of medication nonadherence, especially early declines in adherence, include increased frequencies of rejection, graft loss, and death.