MLC tracking is an emerging technology to improve tumor targeting and reduce normal tissue irradiation during radiotherapy. The purpose of this work is to present the early clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung cancer. Twelve stage 1 lung cancer or lung metastases patients have been recruited into an ethics approved MLC tracking clinical trial (NCT02514512). Each patient has three electromagnetic beacons (Calypso) inserted into the lung surrounding the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5mm from end-exhale tumor volume (GTV). For comparison a conventional motion-encompassing SABR plan was generated with PTV expanded 5mm from a 4DCT-derived internal target volume. Treatment was delivered using a standard linear accelerator using in-house developed software to continuously adapt the MLC motion based on the Calypso beacons’ movement. Tumor motion, treated volume, and reconstructed delivered dose were compared between MLC tracking and conventional motion-encompassing treatment planning. All 46 fractions from the twelve patients have been treated successfully with MLC tracking. The MLC tracking PTV for all patients has been smaller than with ITV based planning (range 12% to 41% reduction, or 2 to 18 cm3 with MLC tracking). Subsequent reductions in normal lung dose were observed. Mean lung dose reduced by up to 30% and on average by 19% (i.e., from 280 cGy to 225 cGy) with MLC tracking compared to ITV-based planning. Tumor motion was seen to vary in motion range during treatment, between fractions and from the planning 4DCT; significantly, larger motion was observed during treatment that exceeded standard PTV boundaries. Reconstruction of delivered treatments confirmed the accurate delivery of MLC tracking, with 100% prescribed dose delivered to the GTV for each of the 46 fractions. The first treatments with MLC tracking have been successfully performed in twelve lung cancer patients. Reductions in treated volumes were observed, which translated to reductions in delivered lung dose.