Introduction: In critically ill patients on mechanical ventilation, the loss of inspiratory and peripheral muscle strength is associated with prolonged mechanical ventilation and failed weaning. Objective: To determine the relationship between handgrip strength and inspiratory muscle strength with the success of the Spontaneous Breathing Trial in adults with ventilatory support greater than 48 hours. Methodology: Prospective observational cross-sectional study performed at a tertiary hospital in Colombia. Handgrip strength and Maximal Inspiratory Pressure were measured once a day before Spontaneous Breathing Trial testing. Pearson’s test and Cohen’s D test were used to analyze correlations. Results: A total of 51 patients were included, 57% male, with a mean age of 51.9±20 years. A positive correlation was identified between Maximal Inspiratory Pressure and grip strength; and a negative correlation between grip strength and Maximal Inspiratory Pressure with the days of stay in the intensive care unit, (r -0.40; p<0.05) and (r -0.45; p<0.05). Conclusions: Handgrip strength and Maximal Inspiratory Pressure were positively correlated with Spontaneous Breathing Trial success. The importance of these measures to guide ventilator disconnection processes is highlighted.