Objective: To analyze clinical features and myopathology changes in muscle fibers, connective tissue, and vessels in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-associated myopathies. Methods: Retrospective review of records and myopathologic features of 49 consecutive patients with myopathies and serum HMGCR antibodies. Results: Clinical features included onset age from 12 to 83 years, female predominance (67%), proximal, symmetric weakness (84%), muscle discomfort (78%), dysphagia (35%), systemic features, including skin rash and interstitial lung disease (37%), statin use (38%), and a high serum creatine kinase (83%). Myopathology included muscle fiber necrosis or regeneration (66%), myonuclear pathology (43%), perimysial connective tissue damage (61%), and lymphocytic foci (27%). Conclusions: Patients with HMGCR antibody-associated myopathies present with weakness and muscle discomfort and often have damage to both perimysial connective tissue and muscle fibers, with necrosis and myonuclear pathology. Only a minority of patients with HMGCR antibody-associated myopathies have a history of statin exposure.