Locus of control as a moderator of the relationship between medication barriers (e.g., side-effects, forgetting to take medication, and keeping track of pills) and anti-hypertensive medication adherence was examined. Baseline data were obtained from 588 hypertensive veterans. In general, fewer medication barriers, higher internal locus of control and lower external locus of control was associated with better hypertensive medication adherence. Furthermore, internal locus of control served as a moderator (beta = -.74, p < .01) for the relationship between medication barriers and medication adherence; effect size was large. Decomposition of the interaction revealed that the relationship between medication barriers and medication adherence was strongest when internal control was high (b = -.24, p < .01). Higher internal locus of control was beneficial when barriers to medication adherence are low, but at high perceived barriers, locus of control plays less of a role in medication adherence. Future efforts to improve medication adherence should consider the patient's perceived level of medication barriers in conjunction with their locus of control.