Objective: To evaluate in vivo changes in the color of esthetic elastomeric ligatures from different manufacturers. Methods: Four widely used commercial brands of elastomeric ligatures were selected and used in 20 adult patients in a split-mouth design. The ligatures were evaluated by orthodontists and patients in a double-blind manner on the day the ligatures were placed (T0) and 30 days after intraoral exposure (T1) by means of a system of staining scores. Groups were compared by Friedman test with p < 0.05. Results: Orthodontists and patients reported similar staining scores (p > 0.05). Results showed that all brands underwent significant staining when exposed to the intraoral environment. Modular-crystal MorelliTM (Sorocaba, SP, Brazil) showed the highest degree of staining with the median reaching the maximum value (3); while the other brands (3M UnitekTM, American OrthodonticsTM and GAC DentsplyTM) showed the median equal to 1 (p < 0.001). A large individual variability in the degree of staining was also found for all brands. Conclusions: All four brands of esthetic ligatures showed significant staining, which appeared to be more pronounced for the MorelliTM brand. Changes in color of the elastomeric ligatures were perceived similarly by patients and orthodontists. The industry needs to improve the color stability of esthetic ligatures.