Background Inverse comorbidity is disease occurring at lower rates than expected among persons with a given index disease. The objective was to identify inverse comorbidity in MS. Methods We performed a combined case-control and cohort study in a total nationwide cohort of cases with clinical onset of MS 1980–2005. We randomly matched each MS-case with five population controls. Comorbidity data were obtained from multiple, independent nationwide registries. Cases and controls were followed from January 1977 to the index date, and from the index date through December 2012. We controlled for false discovery rate and investigated each of eight pre-specified comorbidity categories: psychiatric, cerebrovascular, cardiovascular, lung, and autoimmune comorbidities, diabetes, cancer, and Parkinson's disease. Results A total of 8947 MS-cases and 44,735 controls were eligible for inclusion. We found no inverse associations with MS before the index date. After the index date, we found a decreased occurrence of chronic lung disease (asthma and chronic obstructive pulmonary disease) (HR 0.80 (95% CI 0.75–0.86, p<0.00025)) and overall cancer (HR 0.88 (95% CI 0.81–0.95, p=0.0005)) among MS-cases. Conclusion This study showed a decreased risk of cancers and pulmonary diseases after onset of MS. Identification of inverse comorbidity and of its underlying mechanisms may provide important new entry points into the understanding of MS.