Background: Patients with AML who receive intensive chemotherapy experience immense physical and psychological symptoms, which can result in a substantial deterioration of QOL. As data on the relationship between AML patient coping strategies and patient-reported outcomes are lacking, we aimed to determine the associations between patients’ coping strategies and their quality of life and mood. Methods: We conducted a secondary analysis of cross-sectional data from a multi-site randomized supportive care trial for hospitalized patients diagnosed with AML and receiving intensive chemotherapy. Within 72 hours of initiating chemotherapy, patients completed baseline assessments of QOL (FACT-Leu), anxiety and depression symptoms (HADS), and symptom burden (ESAS). Patients also completed subscales from the Brief Cope to assess baseline use of coping strategies. We created high-order factors (approach-oriented coping vs. avoidant-oriented coping) from the coping subscales and utilized the median split method to identify the proportions of patients with high use of approach and avoidant-oriented coping strategies, respectively. We used linear regression models adjusting for age, gender and diagnosis type (newly diagnosed vs. relapsed/refractory AML) to examine the relationships between patients’ use of coping strategies and their baseline QOL, mood and symptom burden. Results: A total of 160 patients were enrolled in the study (60.0% male; median age 64.4 years [range 19.7-80.1]). Overall, 47.5% (76/160) of patients reported high use of approach-oriented coping strategies, while 38.8% (62/160) reported high use of avoidant-oriented strategies. In regression models, the greater use of approach-oriented coping strategies at baseline was associated with higher baseline QOL (β = 1.33, SE = 0.44, P= 0.003), lower depression (β = -0.28, SE = 0.07, P< 0.001) and anxiety symptoms (β = -0.24, SE = 0.08, P= 0.002), and lower symptom burden (β = -0.96, SE = 0.34, P= 0.006). By contrast, the greater use of avoidant-oriented coping strategies at baseline was associated with lower baseline QOL (β = -4.98, SE = 0.81, P< 0.001), higher depression (β = 0.60, SE = 0.13, P< 0.001) and anxiety symptoms (β = 0.79, SE = 0.14, P< 0.001), and worse symptom burden (β = 2.30, SE = 0.64, P< 0.001). Conclusions: Newly hospitalized patients with AML who utilize approach-oriented coping strategies experience better baseline QOL and mood, and a lower symptom burden. These findings underscore the need for supportive care interventions that promote effective coping in patients with AML, to improve patients’ QOL and reduce their physical and psychological distress.