Background. Patients cite "forgetting" as a reason for nonadherence to highly active antiretroviral therapy (HAART). We measured the effect of a memory-prompting device on adherence to HAART in memory-intact and memory-impaired human immunodeficiency virus (HIV)-infected subjects.Methods. The study was a prospective, randomized, controlled trial involving 64 HIV-infected adults. The intervention was the Disease Management Assistance System (DMAS) device, combined with monthly adherence counseling. Control subjects received only adherence counseling. The DMAS was programmed with HAART regimen data to provide verbal reminders at dosing times. Adherence was measured for 24 weeks using electronic drug exposure monitor (eDEM) caps.Results. A total of 58 subjects completed the 24-week study period; 28 were HAART naive (12 DMAS users and 16 control subjects). Mean adherence scores did not differ significantly between DMAS users (80%) and control subjects (65%). Post hoc analysis of 31 memory-impaired subjects (14 DMAS users and 17 control subjects) revealed significantly higher adherence rates among DMAS users (77%), compared with control subjects (57%) (P=.001). However, analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users (83%), compared with control subjects (77%) (P=.25). At week twelve, 38% of the DMAS users and 14% of the control subjects had an undetectable plasma HIV RNA load (P=.014), and at week 24, the plasma HIV RNA load was undetectable for 34% of the DMAS users and 38% of the control subjects (P=.49). CD4(+) cell counts did not differ between the study arms. Virological and immunological responses were not related to DMAS use in memory-impaired subjects.Conclusion. The DMAS prompting device improved adherence for memory-impaired subjects but not for memory-intact subjects.