Background: The impact of the physician’s (MD) disclosure of PI on the psychological well-being and quality of life (QoL) of clinical trial subjects with terminal disease on Phase I trials has not been formally evaluated. Methods: A prospective cohort of ACP enrolling in phase I trials was assessed at baseline (T1) and one month (T2) utilizing various measures including: state-trait anxiety (STAI-S/T), depression (CES-D), quality of life/QoL (FACIT-Pal), and global health (SF-36). Semi-structured interviews of ACPs also evaluated MD-Pt communication re prognosis and worry about ACP death. Results: 100 subjects (50 Phase I ACPs and 50 SC) were separately interviewed at T1 and T2. For the population as a whole: median age 62 (28-78y); 51% male; 100% married; 88% Ca; 68% > HS educ; 56% GI dx; 54% income <$65,000 yr. At T1, 45% of ACPs acknowledged having a discussion re life expectancy with MD; 35% stated the MD gave a prognostic timeframe; and 41% reported worry re death. For SC at T1, 62% recalled a prognosis discussion with the MD; 50% stated MD gave a timeframe; 53% reported PI disclosure was initiated by the MD; 66% reported worry re ACP death. At T2, rates remained consistent for both ACP and SC with the exception of increased reported worry re ACP death at 55% and 70% respectively. At T2, ACP who denied a prognosis was given by the MD had higher STAI-S (35 ± 10 v 29 ± 9, p=0.03) and CES-D scores (16 ± 12 v 7 ± 4, p=0.01); and lower FACT-Pal scores (128 ± 18 v 153 ± 24, p=0.01). SC with acknowledgement of a prognostic timeframe given by the MD had higher STAI-S anxiety (39 ± 16 v 35 ± 14, p=0.04) at T2. Regression analyses revealed that ACP with acknowledgement of a prognostic timeframe given by the MD had poorer FACIT-Pal QoL over time. Also, SC with acknowledgement of a prognostic timeframe at T2 was negatively associated with SF-36 scores. ACP and SC qualitative responses re PI disclosure revealed salient themes: hope for a positive outcome or prolonged survival; stabilization of disease; emotional distress; ambivalence/fear; acceptance. Conclusions: Physician disclosure of a prognostic timeframe is negatively associated with QoL among clinical trial subjects and SC in phase I trials.