The objective of this study was to assess coronal discoloration induced by the following intracanal medicaments: calcium hydroxide (CH), a mixture of CH paste and chlorhexidine gel (CH/CHX), and triple antibiotic paste (3Mix).Seventy extracted single-canal teeth were selected. Access cavities were prepared and each canal was instrumented with a rotary ProTaper system. The specimens were randomly assigned to CH, CH/CHX, and 3Mix paste experimental groups (n = 20 each) or a control group (n = 10). Each experimental group was randomly divided into 2 subgroups (A and B). In subgroup A, medicaments were only applied to the root canals, while in subgroup B, the root canals were completely filled with medicaments and a cotton pellet dipped in medicament was also placed in the pulp chamber. Spectrophotometric readings were obtained from the mid-buccal surface of the tooth crowns immediately after placing the medicaments (T1) and at 1 week (T2), 1 month (T3), and 3 months (T4) after filling. The ∆E was then calculated. Data were analyzed using 2-way analysis of variance (ANOVA), 3-way ANOVA, and the Scheffé post hoc test.The greatest color change (ΔE) was observed at 3 months (p < 0.0001) and in 3Mix subgroup B (p = 0.0057). No significant color change occurred in the CH (p = 0.7865) or CH/CHX (p = 0.1367) groups over time, but the 3Mix group showed a significant ΔE (p = 0.0164).Intracanal medicaments may induce tooth discoloration. Use of 3Mix must be short and it must be carefully applied only to the root canals; the access cavity should be thoroughly cleaned afterwards.