OBJECTIVE Limb muscle weakness is associated with difficult weaning. However, there are limited data on extubation failure. The objective of this cohort study was to evaluate the association between limb muscle weakness according to the Medical Research Council (MRC) scale and extubation failure rates among patients in a medical intensive care unit (ICU). METHODS All consecutive medical ICU patients who were mechanically ventilated for more than 24 h and who were weaned according to protocol were prospectively registered, and limb muscle weakness was assessed using the MRC scale on the day of planned extubation. Association of limb muscle weakness with extubation failure within 48 h following planned extubation was evaluated with logistic regression analysis. RESULTS Over the study period, 377 consecutive patients underwent planned extubation through a standardized weaning process. Extubation failure occurred in 106 (28.1%) patients. Median scores on the MRC scale for four limbs were lower in patients with extubation failure (14, interquartile range (IQR) 12-16) than in patients without extubation failure (16, IQR 12-18; P = 0.024). In addition, extubation failure rates decreased significantly with increasing quartiles of MRC scores (P for trend <0.001). In multivariable analysis, MRC scores ≤10 points were independently associated with extubation failure within 48 h (adjusted OR 2.131, 95% CI: 1.071-4.240, P = 0.031). CONCLUSIONS Limb muscle weakness assessed on the day of extubation was found to be independently associated with higher extubation failure rates within 48 h following planned extubation in medical patients.