HIV treatment adherence is improved by behavioral interventions, including medication organizers such as pillboxes, which can also interfere with adherence electronic monitoring devices (EMD). This study examined the characteristics of pillbox users and the implications of pillbox use for research using EMD adherence research. Men and women (n = 160) currently taking antiretroviral medications (ARVs) completed anonymous surveys in a community research setting. Sixty-three (39%) of individuals taking ARVs were currently using a pillbox. Pillbox users were significantly more likely to have an undetectable viral load and less likely to have missed their medications within a day of the assessment. Pillbox users indicated feeling that they benefited from using their pillbox and 76% reported they would likely stop using their pillbox if required to participate in a research study that paid them. Adherence EMD pose methodological limitations to research when pillbox users are excluded and ethical implications when pillbox users stop using their pillbox to participate.