Abstract Background Excessive respiratory muscle effort during mechanical ventilation may cause patient self-inflicted lung injury and load-induced diaphragm myotrauma, but there are no non-invasive methods to reliably detect elevated transpulmonary driving pressure and elevated respiratory muscle effort during assisted ventilation. We hypothesized that the swing in airway pressure generated by respiratory muscle effort under assisted ventilation when the airway is briefly occluded (ΔP_occ) could be used as a highly feasible non-invasive technique to screen for these conditions. Methods Respiratory muscle pressure (P_mus), dynamic transpulmonary driving pressure (ΔP_L,dyn, the difference between peak and end-expiratory transpulmonary pressure), and ΔP_occ were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict ΔP_L,dyn and P_mus from ΔP_occ was derived and validated using cross-validation. External validity was assessed in an independent cohort (Nanjing, China). Results Fifty-two daily recordings were collected in 16 patients. In this sample, P_mus and ΔP_L were frequently excessively high: P_mus exceeded 10 cm H₂O on 84% of study days and ΔP_L,dyn exceeded 15 cm H₂O on 53% of study days. ΔP_occ measurements accurately detected P_mus > 10 cm H₂O (AUROC 0.92, 95% CI 0.83–0.97) and ΔP_L,dyn > 15 cm H₂O (AUROC 0.93, 95% CI 0.86–0.99). In the external validation cohort (n = 12), estimating P_mus and ΔP_L,dyn from ΔP_occ measurements detected excessively high P_mus and ΔP_L,dyn with similar accuracy (AUROC ≥ 0.94). Conclusions Measuring ΔP_occ enables accurate non-invasive detection of elevated respiratory muscle pressure and transpulmonary driving pressure. Excessive respiratory effort and transpulmonary driving pressure may be frequent in spontaneously breathing ventilated patients.