PurposeThis study aims to evaluate the viability of utilizing the Structural Similarity Index (SSI*) as an innovative imaging metric for quality assurance (QA) of the multi‐leaf collimator (MLC). Additionally, we compared the results obtained through SSI* with those derived from a conventional Gamma index test for three types of Varian machines (Trilogy, Truebeam, and Edge) over a 12‐week period of MLC QA in our clinic.MethodTo assess sensitivity to MLC positioning errors, we designed a 1 cm slit on the reference MLC, subsequently shifted by 0.5–5 mm on the target MLC. For evaluating sensitivity to output error, we irradiated five 25 cm × 25 cm open fields on the portal image with varying Monitor Units (MUs) of 96–100. We compared SSI* and Gamma index tests using three linear accelerator (LINAC) machines: Varian Trilogy, Truebeam, and Edge, with MLC leaf widths of 1, 0.5, and 0.25 mm. Weekly QA included VMAT and static field modes, with Picket fence test images acquired. Mechanical uncertainties related to the LINAC head, electronic portal imaging device (EPID), and MLC during gantry rotation and leaf motion were monitored.ResultsThe Gamma index test started detecting the MLC shift at a threshold of 4 mm, whereas the SSI* metric showed sensitivity to shifts as small as 2 mm. Moreover, the Gamma index test identified dose changes at 95MUs, indicating a 5% dose difference based on the distance to agreement (DTA)/dose difference (DD) criteria of 1 mm/3%. In contrast, the SSI* metric alerted to dose differences starting from 97MUs, corresponding to a 3% dose difference. The Gamma index test passed all measurements conducted on each machine. However, the SSI* metric rejected all measurements from the Edge and Trilogy machines and two from the Truebeam.ConclusionsOur findings demonstrate that the SSI* exhibits greater sensitivity than the Gamma index test in detecting MLC positioning errors and dose changes between static and VMAT modes. The SSI* metric outperformed the Gamma index test regarding sensitivity across these parameters.