Objective: To study the clinical effect of thymectomy in a well-defined early-onset MG subgroup and to correlate it to MG severity, the presence of circulating muscle autoantibodies, and the need for pharmacological treatment in a long-term setting. Methods: Fifty-two consecutive AChR antibody-positive early-onset MG patients (34 thymectomized and 18 nonthymectomized) were included. Severity was assessed and the pharmacological treatment monitored on a yearly basis, starting from the year of MG onset, for 5, 10, 15, and 20 consecutive years; AChR, titin, and RyR antibodies were assayed. Results: In the four follow-up groups, MG severity was significantly higher in nonthymectomized compared to thymectomized MG patients. The postthymectomy MG improvement was significant and persistent. There were 21/34 remissions in thymectomized patients and only 4/18 in the nonthymectomized group. Patients with initially high or low AChR antibody concentration had a similar thymectomy outcome. Only 6 patients had titin antibodies, and none had RyR antibodies. Conclusion: The present study indicates a benefit of thymectomy in early-onset MG. The muscle autoantibody concentration does not influence the outcome of thymectomy in early-onset MG.