BACKGROUND: Delays in the mechanical ventilation (MV) weaning process increase mortality. The spontaneous breathing test is the gold standard to assess weaning and extubation success, although it has approximately 85% accuracy. Studies have demonstrated a correlation between decreased heart rate variability (HRV) and weaning failure. OBJECTIVES: To assess the usefulness of HRV as a predictor of MV weaning outcomes. METHODS: Cross-sectional analytical study in adults of both sexes on MV in intensive care unit (ICU) stay. Patients were divided into weaning success and failure groups. Clinical data were collected, and HRV records were obtained with a heart rate monitor. RESULTS: The study included 68 individuals - 91.1% in the weaning success group and 8.9% in the failure group. All HRV indices analyzed in both groups were lower than the reference values. No statistical difference was found in the mean RR interval (RRi), the standard deviation of the NN interval (SDNN), and the square root of the mean squared differences of successive NN intervals (RMSSD) between the groups. The weaning failure group had a significant increase in LF (41 vs. 69.4) and LF/HF ratio (0.685 vs. 2.6) and a significant decrease in HF (58.85 vs. 30.2). CONCLUSIONS: HRV measure with spectral analysis can be a good predictor of MV weaning failure. Integrating this assessment tool in ICU to predict weaning outcomes could provide more precise prognoses and more adequate assistance quality.