OBJECTIVE: To investigate the feasibility of active heart sparing (AHS) planning in patients with locally advanced and centrally located NSCLC receiving standard definitive radiotherapy (RT), while maintaining or improving appropriate lung, esophagus, and spinal cord constraints and planning target volume (PTV) coverage intent. METHODS AND MATERIALS: A total of 27 patients with stage IIIA/B NSCLC treated with curative intent RT were selected for this analysis. All existing radiation plans were revised and 27 further new equivalent plans were calculated using AHS for the same cohort of patients. Primary end-point was feasibility of AHS using constraints for heart substructures. The secondary end point was to calculate the difference in terms of dosimetric parameters of heart substructures and principal OARs as well as PTV-coverage parameters within the current patient group. RESULTS: AHS was feasible in the entire group of patients. An optimal coverage of the target volume was obtained and all mandatory constraints for OARs have been met. The median value of the mean heart dose (MHD) was 8.18 Gy and 6.71 Gy in the standard planning group and AHS-group, respectively (p = 0.000). Other heart parameters such as V CONCLUSION: Our analysis showed an improvement of dosimetric parameters of the heart and heart substructures in patients affected by locally advanced and centrally located NSCLC treated with curative RT using AHS optimization. This approach could lead to a possible reduction of heart events and a prolonged survival. New clinical studies regarding RT in advanced NSCLC should include cardiologic evaluations and biomarkers as well as the contouring of cardiac substructures.