This study assessed the effects on quality of life (QoL) of dobutamine-atropine stress echocardiography (DASE) and electrocardiogram exercise testing (EET) accelerated diagnostic protocols for early stratification of low-risk patients with acute chest pain (ACP). A total of 290 patients with ACP, a nondiagnostic electrocardiogram, and negative biomarkers were randomly assigned to an accelerated diagnostic protocol (DASE, n = 110, or EET, n = 89) or usual care (n = 91) and followed up for 2 months. QoL was assessed at discharge and 2-month follow-up using the Nottingham Health Profile questionnaire. Baseline and 2-month follow-up answers to the Nottingham Health Profile questionnaire were available for 207 patients (71%; 55 in the usual-care, 77 in the DASE, and 75 in the ETT arm). At predischarge, patients in the usual-care arm reported higher impairment in the physical mobility and pain dimensions compared with the DASE and EET arms (p = 0.019 and p = 0.023, respectively). At 2-month follow-up, QoL improved in all groups; however, patients in the usual-care arm had significantly worse scores than patients managed using accelerated diagnostic protocols in the physical mobility, pain, social isolation, emotional reactions, and energy level dimensions (p = 0.014, p = 0.002, p = 0.04, p = 0.01, and p = 0.003, respectively). In conclusion, low-risk patients with ACP had non-negligible impairment of QoL in the acute phase. Emergency department ADPs with early DASE and EET reduced QoL impairment at both baseline and 2-month follow-up.