The objective of this study was to determine factors associated with pyridostigmine therapy in patients with ocular myasthenia gravis (OMG). This retrospective study included eighty-five patients with OMG who have been treated with pyridostigmine. Patients were excluded if they were diagnosed as generalized myasthenia gravis within a month after diagnosis or were treated with other medications. Forty-two patients responded to pyridostigmine and 43 patients did not. There were no significant differences in gender, age, the duration of symptoms before treatment, the dosage of pyridostigmine, and the initial presentations of ptosis or diplopia between the two groups. However, an initial presentation of concurrent ptosis and diplopia and the presence of systemic involvement after follow up were significant factors associated with an insensitivity to pyridostigmine in patients with OMG (p = 0.001 and p = 0.01, respectively). Determining these factors could help predict the pyridostigmine response in patients with OMG.