(1) Background: Job burnout may affect the prognosis of patients with acute coronary syndrome (ACS) through mechanisms involving heart rate variability (HRV). However, no study has yet examined those potential associations. Hence, we conducted the present study to investigate this issue. (2) Method: Participants included patients who presented with a first episode of ACS and who were employed. The Copenhagen Burnout Inventory (CBI) was used to assess job burnout. Twenty-four-hour ambulatory electrocardiography recorded HRV on four occasions, i.e., during the hospitalization and follow-ups at one, six, and 12 months, respectively. (3) Results: A total of 120 participants who at least completed three Holter examinations throughout the study were enrolled in the final analysis. Job burnout scores at baseline were inversely associated with LnSDNN, LnTP, LnHF, LnLF, LnULF, and LnVLF during the consequent one-year follow-up. Each 1 SD increase in job burnout scores predicted a decline ranging from 0.10 to 0.47 in the parameters described above (all p < 0.05), and all relationships were independent of numerous confounders, including anxiety and depression. (4) Conclusion: High job burnout predicted reduced HRV parameters during the one-year period post-ACS in the working population.