OBJECTIVES: We sought to 1) examine the association between serious psychological distress (SPD) and emergency department (ED) use among adults with multimorbidity in the US and 2) investigate the association between SPD and the reasons for ED use. METHODS:  A cross-sectional, retrospective, observational study design was conducted using data from the 2014 National Health Interview Survey (NHIS). The study sample consisted of 13,708 US adults with multimorbidity. Chi-square tests were used to examine unadjusted subgroup differences. Multivariable logistic regression models were used to assess the association between SPD and ED use. Among ED users, adjusted logistic regression models were conducted to examine the association between SPD and the reasons for the ED use in the past 12 months. RESULTS: After controlling for other variables, adults with SPD were more likely to use ED than those without SPD (AOR = 1.73, 95% CI = 1.40, 2.15). Among ED users, we found that adults with SPD were more likely (AOR = 1.43, 95% CI = 1.03, 1.98) to report “the clinic was not open” as the reason for using ED than those without SPD. CONCLUSIONS:  Combination of SPD and multimorbidity was associated with higher ED use. Inconvenient clinic hours were more likely to be reported by adults with SPD as the reason for their ED use. Management programs addressing SPD among adults with multimorbidity are needed to minimize the risk of ED use.