Background: Prior research identifies marriage as a protective resource for couples during the cancer trajectory. However, the prevalence of potential MD and its effect on the quality of life (QOL) and psychological morbidity of ACP in Phase I trials has not been described. Methods: A prospective cohort of ACP enrolling in phase I trials was assessed at baseline (T1) and one month (T2) using the following measures: depression (CES-D), state-trait anxiety (STAI-S/T), quality of life/qol (FACIT-Pal), global health (SF-36), and marital satisfaction (DAS). Semi-structured interviews evaluated ACP-SC experiences re MD including: fulfillment, contentment, intimacy, conflict. Results: To date, a total of 54 married phase I ACP-SC couple dyads (n=108 subjects) were separately interviewed at T1 and T2. For the total population: median age 60y (28-78y); 50% male; 88% Ca; 68%> HS educ; 57% GI dx; 52% income <$65,000 yr. Couples were married on average for 37y (15-50y) and 18% ACPs reported this was a second marriage. At T1, 45% of ACP reported marital fulfillment; 37% reported marital contentment; 67% reported intimacy concerns; 65% reported marital conflict. For SC at T1, 31% reported marital fulfillment; 50% reported marital contentment; 74% SC reported intimacy concerns; and 79% reported marital conflict. Rates remained stable for both ACP and SC with the exception of increased self-reported marital conflict at 68% and 83% respectively at T2. At T2, ACP who reported marital conflict had higher STAI-S (33 ± 10 v 28 ±12, p=0.01) and CES-D (13 ± 12 v 11 ± 9, p=0.03). SC with self-reported marital conflict had higher STAI-S anxiety (39 ± 17 v 35 ± 13, p=0.03) at T2. In regression analyses, ACP with intimacy concerns had poorer FACIT-Pal QOL over time. Also, SC with intimacy concerns at T2 was negatively associated with SF-36 and DAS scores over time. ACP and SC qualitative inquiry re MD exposed various themes: conflicts re EOL tx/advanced directives/estate planning; lack of physical/emotional intimacy; non-existent sex life; lack of communication. Conclusions: MD is negatively associated with QOL among clinical trial subjects and SC in phase I trials.