Re-worsening left ventricular ejection fraction (LVEF) is observed in some patients with dilated cardiomyopathy (DCM) despite initial improvements in LVEF. We analyzed cardiac outcomes and clinical variables associated with this re-worsening LVEF. A total of 180 newly diagnosed DCM patients who received only pharmacotherapy were enrolled. Echocardiography was performed after 6, 12, 24, and 36 months after initiation of pharmacotherapy. Patients were divided into three groups: (1) Improved: (n = 113, 63%), defined as those > 10% increase in LVEF after 12 months and no decrease (> 10%) between 12 and 36 months; (2) Re-worse: (n = 12, 7%), those with > 10% increase in LVEF after 12 months but with decrease (> 10%) between 12 and 36 months; and (3) Not-improved: (n = 55: 30%), those with no increase in LVEF (> 10%) after 12 months. Patients with re-worse group were older (P = 0.04) and had higher brain natriuretic peptide (BNP) levels after 12 months (P = 0.002) than those in the Improved group. Major cardiac events (sudden death, implantation of a ventricular assist device, and death due to heart failure,) were observed in 13 (7%) patients after 36 months of pharmacotherapy. Multivariate analysis revealed that the Re-worse group had a higher risk for cardiac events (hazard ratio 11.7, 95% confidence interval 1.9–90.7, P = 0.01) than the Improved group, but had a similar risk compared with the Not-improved group. Re-worsening LVEF was associated with poor cardiac outcomes in newly diagnosed DCM patients. Age and persistently high-BNP levels after improvement in LVEF were significantly associated with re-worsening LVEF.