Background Measurement of respiratory mechanics during non-invasive ventilation (NIV) precludes use of the traditional airway flow sensor. Increasing use of NIV in premature infants necessitated novel instrumentation for measuring airflow without interfering with the nasal/oral interface. Respiratory inductance plethysmography (RIP), in addition to providing chest wall motion analysis, may be used for volume and airflow measurements when properly calibrated. Objective To develop an efficient RIP calibration technique to allow bedside measurement of respiratory mechanics and to validate it’s accuracy against traditional pneumotachometer (PNT) measurements while simultaneously computing thoracoabdominal asynchrony indices in premature infants. Design/methods RIP ribcage and abdominal signals were recorded simultaneously with facemask PNT signals. RIP was calibrated by qualitative diagnostic calibration and multiple linear regression algorithms on artefact-free breaths with amplitudes within the mean±1SD. A sequence of optimising iterations for computer breath selection produced best-fit regression coefficients with the PNT flow. Transpulmonary pressure was measured by esophageal catheter. Lung compliance and airway resistance were computed by a least mean square technique. Ribcage to abdominal phase angle (phi), Laboured breathing index (LBI), and phase relation in total breath (PhRTB) were computed from analysis of RIP ribcage and abdomen excursions. Validation measurements were performed on 18 infants of 28–35wks GA. Results Correlation coefficients for compliance and resistance by PNT vs. RIP were r 2 =0.9737 and 0.8980 respectively. LBI for these infants was 1.2 ± 0.6, phi was 54.4 ± 7.4 degrees and PhRTB was 33.4 ± 3.1%. Conclusion When properly calibrated, RIP derived respiratory mechanics measurements provide sufficient diagnostic accuracy in infants receiving NIV support.