BACKGROUND Studies show that fluoride (F) and nano-hydroxyapatite (nano-HA) would result in remineralization of white spot lesions (WSLs), which are among the most prevalent consequences of fixed orthodontic treatment. The present study evaluates and compares the clinical effects of an Iranian toothpaste containing nano-HA with F-containing one on early enamel lesions. METHODS In this randomized clinical trial study, 50 patients who had received fixed orthodontic treatment were recruited immediately after debonding. Three photographs, including frontal, lateral right and left views of occlusion, were obtained. Moreover, surfaces with WSLs were recorded using DIAGNOdent. Plaque index of each patient determined using disclosing agents. At first visit, each patient was asked to select one type of toothpaste (nano-HA containing vs. F containing named A or B), randomly and were instructed how to brush their teeth (25 patients in each group). Examination was done at 1, 3, and 6 months' intervals. Finally, photographs were analyzed by Digimizer (V5) software, and the lesion extent was recorded in pixels. SAS 9.4 was used to analyze data and was set at 0.05. RESULTS According to data, lesion extent showed a significant decrease (P < 0.001). At baseline, the difference between the two groups regarding the lesion extent was 268 pixels while it dropped to 89 pixels after 6 months. DIAGNOdent results showed that at baseline, fluorescence difference was 0.3 while it reached the number of 0.8 after 6 months, indicating the outperformance of nano-HA containing toothpaste. CONCLUSIONS The Iranian nano-HA containing toothpaste performed better than F-containing one in terms of the amount of remineralization and diminishing the lesion extent.