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Multiple sclerosis (MS) is a neurological disorder that progressively distorts the myelination of axons within the central nervous system (CNS). Increased core body temperature or metabolism as a result of exercise are common causes of short-term exacerbations of neurological symptoms in MS. About 60–80% of patients with MS experience a worsening of their symptoms when exposed to heat. In comparison, less data are available on the relationship between ambient meteorological conditions (e.g., temperature and relative humidity (RH)) and fluctuations in such variables in relation to MS symptoms. Thus, this study examined associations between time-lagged exposure to meteorological conditions and risk of a clinic visit due to MS among US veterans between 2010 and 2013. This study leveraged data from the Veterans Affairs (VA) and National Climactic Data Center (NCDC) for the continental US, partitioned into eight climate zones. We used a case crossover design to assess the risk of a MS clinic visit with respect to several meteorological conditions. Location-specific time-lagged daily (ambient) exposure to temperature, RH, and temperature variations (standard deviation (SD) of temperature) were computed (up to 30 days) for each case (i.e., day of MS visit) and control (a randomly assigned date ± 90–270 days prior to visit). Statistical analyses were conducted to examine independent associations between the selected meteorological conditions and risk of MS visits at the national and regional levels. A total of 533,066 patient visits received a MS diagnosis (International Classifications of Diseases (ICD)-9 code = 340). The Northeast (NE) and Upper Midwest (UMW) regions reported the highest frequency of clinic visits due to MS. Clinic visits were 9% more likely to occur in the spring, summer, and fall months (March–October) than in the winter (OR = 1.089; 95% CI = 1.076–1.103; p < 0.01). In the univariate analyses, the SD of temperature, temperature, and temperature–RH interaction were positively associated with an elevated risk of a MS clinic visit, while the RH was negatively associated with the risk for a clinic visit. In multivariate analyses, the strongest association of a MS clinic visit was observed with the SD of the temperature (OR = 1.012; 95% CI 1.008–1.017; p < 0.01). These associations between MS clinic visits and meteorological conditions varied across climate regions, with the strongest associations being observed in the LMW, UMW, DSW, and NE zones. The SD of the temperature was again the strongest associated predictor when examined regionally. Temperature variations and temperature–RH interactions (a proxy of the heat index) showed significant associations with MS clinic visits. These associations varied across climate regions when examined geographically. Our findings have implications for the management of MS in severe or recurrent cases, especially considering the impending changes in the daily temperature variations and intensity of the heatwaves expected with the intensification of global warming.