A persistent non-treponemal serological response can be observed in patients with syphilis after treatment and is referred to as serofast. This status makes it difficult for clinicians to judge the curative effect of treatment, particularly in patients with early syphilis. In the present study, a total of 114 eligible serofast patients treated between January 2009 and June 2016 were retrospectively analyzed. All patients were subjected to rapid plasma reagin (RPR) serological tests and followed up for 24 months. The patients who remained serofast after initial therapy were given the first retreatment, and at 12 months, those who were still serofast received a second retreatment. After the first retreatment (6 months), 33.3% of the subjects (38/114) were serologically cured (≥4-fold decline in RPR titer). At 24 months, the patients that had achieved serological cure accounted for 23.7% (18/76) of the patients that received the second retreatment. Furthermore, 26.3% of subjects that achieved serological cure (10/38) and had not been further treated after the first retreatment spontaneously presented with a ≥4-fold decline in RPR titer or negative status. In conclusion, the present study indicated that in patients with early syphilis and serofast status after initial treatment, retreatments may not provide any significant benefit. The second retreatment did not significantly improve the patient's serological cure rate. There is no evidence that patients with early syphilis and serofast should receive multiple retreatments, in spite of this being commonly performed in clinical practice.