Existing volumetric modulated arc therapy (VMAT) optimization using coplanar arcs is highly efficient but usually dosimetrically inferior to intensity modulated radiation therapy (IMRT) with optimized non-coplanar beams. To achieve both dosimetric quality and delivery efficiency, we proposed in this study, a novel integrated optimization method for non-coplanar VMAT (4πVMAT). 4πVMAT with direct aperture optimization (DAO) was achieved by utilizing a least square dose fidelity objective, along with an anisotropic total variation term for regularizing the fluence smoothness, a single segment term for imposing simple apertures, and a group sparsity term for selecting beam angles. Continuous gantry/couch angle trajectories were selected using the Dijkstra's algorithm, where the edge and node costs were determined based on the maximal gantry rotation speed and the estimated fluence map at the current iteration, respectively. The couch–gantry–patient collision space was calculated based on actual machine geometry and a human subject 3D surface. Beams leading to collision are excluded from the DAO and beam trajectory selection (BTS). An alternating optimization strategy was implemented to solve the integrated DAO and BTS problem. The feasibility of 4πVMAT using one full-arc or two full-arcs was tested on nine patients with brain, lung, or prostate cancer. The plan was compared against a coplanar VMAT (2πVMAT) plan using one additional arc and collimator rotation. Compared to 2πVMAT, 4πVMAT reduced the average maximum and mean organs-at-risk dose by 9.63% and 3.08% of the prescription dose with the same target coverage. R50 was reduced by 23.0%. Maximum doses to the dose limiting organs, such as the brainstem, the major vessels, and the proximal bronchus, were reduced by 8.1 Gy (64.8%), 16.3 Gy (41.5%), and 19.83 Gy (55.5%), respectively. The novel 4πVMAT approach affords efficient delivery of non-coplanar arc trajectories that lead to dosimetric improvements compared with coplanar VMAT using more arcs. [ABSTRACT FROM AUTHOR]