Occlusions of the middle cerebral artery (MCA) M2 segments can be difficult to address with mechanical thrombectomy (MTB) using standard projections and this can affect the final recanalization. Three-dimensional rotational angiography (3D-RA) allows to obtain a 3D model of cerebral vessels in a few seconds and to determine the best two-dimensional (2D) projections to be selected to evaluate and treat cerebrovascular diseases, such as aneurysms or vascular malformations. We aimed to determine if 3D-RA could be applied also in MTB. A retrospective review of two patient cohorts treated during two time periods of 12 months before and after the introduction of 3D-RA use at our institution for MTB in M2 occlusions. Analyses were conducted to compare the two groups for procedural characteristics, such as timing, recanalization rate and complications and clinical outcome. One hundred acute ischaemic stroke (AIS) patients (3D-RA group = 57; controls = 43) underwent MTB for an M2 occlusion during the two study periods. Recanalization rates were significantly higher in cases treated with 3D-RA. The mean 3D technique thrombectomy time was compared to that of non-3D cases (47 vs. 49 min, respectively). Our findings showed that 3D-RA is a useful tool to select specific working projections to AIS patients presenting an M2 occlusion by improving final recanalization compared to standard projections, without increasing the overall procedural time.