Objective: Previous studies have reported a possible prodrome in multiple sclerosis (MS) defined by non-specific symptoms including mood disorder or genito-urinary symptoms and increased health care use detected several years before diagnosis. This study aimed to evaluate agnostically the associations between diseases and symptoms diagnosed in primary care and the risk of multiple sclerosis (MS) relative to controls and two other autoimmune inflammatory diseases with similar population characteristics, namely lupus and Crohn’s disease. Methods: A case-control study was conducted using electronic health records from the Health Improvement Network database in the UK and France. We agnostically assessed the associations between 113 diseases and symptoms in the five years before and after diagnosis in patients with subsequent diagnosis of MS. Individuals with a diagnosis of MS were compared to individuals without MS, and individuals with two other auto-immune diseases, Crohn’s disease and lupus. Results: The study population consisted of patients with MS (n= 20,174), patients without MS (n=54,790), patients with Crohn’s disease (n=30,477) or patients with lupus (n=7,337). Twelve ICD-10 codes were significantly positively associated with the risk of MS compared to controls without MS. After considering ICD-10 codes suggestive of neurological symptoms as the first diagnosis of MS, five ICD-10 codes remained significantly associated with MS: depression (UK OR 1.22 [95%CI 1.11-1.34]), sexual dysfunction (1.47 [1.11-1.95]), constipation (1.5 [1.27-1.78]), cystitis (1.21 [1.05-1.39]), and urinary tract infections of unspecified site (1.38 [1.18-1.61]). However, none of these conditions was selectively associated with MS in comparisons with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the five years after diagnosis. Conclusion: We identified 5 health conditions associated with subsequent MS diagnosis, which may be considered not only prodromal but also early-stage symptoms. However, these health conditions overlap with prodrome of two other autoimmune diseases, hence lacking specificity to MS.