Objective: Past studies have shown common pathologic characteristics and shared immunologic features between polymyositis (PM) and amyotrophic lateral sclerosis (ALS). To explore the potential relationship between the 2 diseases, we performed a nationwide cohort study., Methods: We identified all newly diagnosed patients with PM from Taiwan's Registry of Catastrophic Illness Database between January 1, 1998 and December 31, 2011. Each PM patient was matched to ≤5 control patients from the National Health Insurance Research Database by sex, age, and entry date. Cumulative incidence of ALS was calculated by the Kaplan-Meier method and compared using the log rank test. Cox hazard regression was used to calculate the hazard ratio of ALS., Results: A total of 1,778 PM patients and 8,124 control patients were enrolled. PM patients had a higher cumulative incidence of ALS (P < 0.001). There was a positive correlation in being diagnosed with ALS in patients previously diagnosed with PM when stratified by sex. Consistent trends were conserved across different age strata. The strength of this association remained statistically significant after adjusting for sex, age, and concomitant autoimmune diseases (hazard ratio 25.72 [95% confidence interval 2.95-224.58]; P = 0.003)., Conclusion: This study demonstrates that a diagnosis of PM increased the likelihood of a subsequent ALS diagnosis, independent of sex, age, and concomitant autoimmune diseases. Future studies are warranted to clarify the underlying biologic mechanisms and to translate them into clinical therapeutic options., (© 2016, American College of Rheumatology.)