Background: Diaphragmatic excursion is a crucial predictor of extubation outcomes in subjects on mechanical ventilation. However, its measurement can be influenced by various factors, which leads to inconsistent optimal thresholds and accuracy. Tissue Doppler imaging variables of the diaphragm have been established as reliable indicators for predicting extubation outcomes. This study aimed to assess the predictive ability of combining diaphragmatic excursion with tissue Doppler imaging variables of the diaphragm in subjects on mechanical ventilation. Methods: This prospective observational study was conducted from April 2023 to April 2024, eligible subjects who underwent mechanical ventilation for > 48 h and successfully completed a 30-min spontaneous breathing test in the ICU of our center. Diaphragmatic excursion and tissue Doppler imaging variables (including peak contraction velocity, peak relaxation velocity, maximal contraction rate, and maximal relaxation rate) were assessed immediately after a 30-min spontaneous breathing trial. The subjects were categorized into successful extubation and failed extubation groups based on their extubation outcomes. Differences in diaphragmatic ultrasound variables between these groups were analyzed. Results: The study included 63 subjects in the successful extubation group and 28 subjects in the failed extubation group. The area under the receiver operating characteristic curve for diaphragmatic excursion in predicting successful extubation was determined as 0.79 (95% CI, 0.69 ∼ 0.89), with a sensitivity of 82.5% and a specificity of 75.0%. The combined area under the receiver operating characteristic curve for diaphragmatic excursion and tissue Doppler imaging variables (including peak contraction velocity and maximal relaxation rate) in predicting successful extubation was determined as 0.94 (95% CI, 0.88 ∼ 0.99), with a sensitivity of 92.1% and a specificity of 89.3%. Conclusions: Combining diaphragmatic excursion with tissue Doppler imaging variables of the diaphragm enhanced the prediction of extubation outcomes in the subjects on mechanical ventilation compared with diaphragmatic excursion alone.