Background <p>The 2024 McDonald criteria for multiple sclerosis (MS) introduced novel biomarkers (central vein sign, paramagnetic rim lesion, kappa free light chain) alongside conventional updates. However, access to these novel markers is regionally limited, making the conventional components the most feasible option in many clinical settings. Yet real-world evidence on their diagnostic performance remains limited, prompting this evaluation in Chinese patients with suspected MS.</p> Methods <p>We retrospectively enrolled 184 patients aged 12–50&#xa0;years with a first central nervous system demyelinating event or atypical presentation with MS-suspicious imaging, and lesions in ≥ 2 of 5 anatomical regions. Diagnostic assessments were performed per the 2017 and 2024 criteria.</p> Results <p>The 2024 criteria identified 173 patients (94.0%) versus 166 (90.2%) by the 2017 criteria (<i>p</i> = 0.023), with substantial concordance (<i>κ</i> = 0.739). The 2024 criteria yielded seven additional diagnoses, including two with 4–5 regions without the need for dissemination in time (DIT), three fulfilling dissemination in space (DIS) via the optic nerve as the fifth region, and two atypical presentation cases diagnosed by DIS plus DIT. The 2024 criteria significantly reduced required clinical attacks (<i>p</i> = 0.037). While median diagnostic time did not differ significantly (<i>p</i> = 0.058), five patients achieved markedly earlier diagnosis (median advance 47&#xa0;months). Subgroup analysis showed a higher diagnostic rate in patients with a single clinical attack (<i>p</i> = 0.041).</p> Conclusion <p>Even without novel biomarkers, the conventional components of the 2024 criteria improved sensitivity in high-lesion burden or atypical cases—a conservative estimate supporting real-world clinical use in China.</p>