To characterize predictors of impairment in research decision-making capacity, we undertook a direct comparison of schizophrenia/schizoaffective (n=52), medically ill (diabetic; n=51), and non-ill (n=57) subjects. Scores on the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) were correlated with demographic variables and scores on the Positive and Negative Syndrome Scale (PANSS), Mini-Mental State Examination (MMSE), and Short-Form-36 (SF-36). Across diagnoses, cognitive capacity, physical functioning, and a diagnosis of mental illness had the greatest impact on decision-making capacity, with level of education also having an impact. 69-89% of schizophrenia/schizoaffective subjects attained MacCAT-CR subscale scores achieved by almost all comparison (98-100%) and medically ill (94-100%) subjects. Positive, negative, and general psychotic symptoms correlated with poorer scores. Prior research experience, number of queries used during interview, and emotional functioning also predicted MacCAT-CR scores. These data suggest that investigators and IRBs should consider a number of variables, many of which reach across diagnoses, as they decide which populations and individual subjects may require more intensive screening for decisional impairment or educational interventions to improve their abilities to make capable decisions about research participation.