Purpose To demonstrate different topographic distributions of multiple-evanescent white dot syndrome (MEWDS) and secondary MEWDS disease and to describe possible associations. Methods Clinical evaluation and multimodal retinal imaging in 27 subjects with MEWDS (29 discrete episodes of MEWDS). Ophthalmic assessment included best-corrected visual acuity testing and multimodal retinal imaging with OCT, blue-light autofluorescence, fluorescein and indocyanine green angiography, fundus photography, and widefield pseudocolor and autofluorescence fundus imaging. Results The topographic distribution of MEWDS lesions was centered on or around the optic disc (n = 17, 59%), centered on the macula (n = 7, 24%), sectoral (n = 2, 7%), or was indeterminate (n = 3, 10%). The MEWDS episodes either occurred in the absence ('primary MEWDS'; n = 14, 48%) or presence of concurrent chorioretinal pathology ('secondary MEWDS'; n = 15, 52%). In patients with the latter, MEWDS lesions were often centered around a coexisting chorioretinal lesion. The majority of patients in both groups experienced resolution of their symptoms and retinal changes on multimodal imaging by 3 months. Conclusions Distinct distributions of MEWDS lesions were identified. MEWDS may occur in tandem with other chorioretinal pathology, which may impact the topography of MEWDS lesions. Key messages center dot MEWDS frequently occurs with concurrent chorioretinal pathology. center dot Different distributions of MEWDS lesions exist, and chorioretinal pathology may determine the topography of MEWDS lesions. center dot Multimodal imaging is often vital for diagnosing MEWDS, particularly where concurrent chorioretinal pathology and/or high myopia are present. center dot Widefield autofluorescence imaging allows for determining the topographic distribution of MEWDS lesions.