Ventilation weaning is a key intensive care event influencing preterm infants’ discharge from a neonatal intensive care unit (NICU). Osteopathic manipulative treatment (OMT) has been recently introduced in some Italian NICUs. This retrospective cohort study tested if OMT is associated with faster non-invasive ventilation (NIV) weaning. The time to NIV weaning was assessed in very preterm and very low birth weight infants who either received or did not receive OMT. The propensity score model included gender, antenatal steroids, gestational age (GA), birth weight (BW), and Apgar score 5′. Out of 93 infants, 40 were included in the multilevel survival analysis, showing a reduction of time to NIV weaning for GA (HR: 2.58, 95%CI: 3.91 to 1.71, p < 0.001) and OMT (HR: 3.62, 95%CI: 8.13 to 1.61, p = 0.002). Time to independent ventilation (TIV) was modeled with GA and BW as dependent variables and OMT as the factor. A negative linear effect of GA and BW on TIV was shown. OMT exposure studied as the factor of GA had effects on TIV in infants born up to the 32nd gestational week. Preterm infants exposed to OMT were associated with earlier achievement of NIV weaning. This result, together with the demonstrated OMT safety, suggests the conduct of clinical trials in preterm infants younger than 32 weeks of GA.