Background and Objectives: Tooth whitening is a relatively conservative and effective option to treat discolored teeth. However, questions remain whether in-office or at-home tooth whitening products with short treatment durations are as effective and stable as products with longer treatment durations.Materials and Methods: Forty human third molars with intact enamel surfaces were divided into four groups of ten each, subjected to discoloration challenges with coffee for 60 h, and they were treated with four professional tooth whitening systems: two for take-home use—6% hydrogen peroxide for 30 min/d for a total of 7 h in 14 days (HP6), 10% carbamide peroxide for 10 h/d for 140 h in 14 days (CP10), as well as two for in-office use—35% HP for 10 min × 3 (HP35) for a total of 30 min and 40% HP for 20 min × 3 (HP40) for a total of 60 min. Teeth colors were assessed in the CIE L*a*b* color space with a spectrophotometer immediately and six months after whitening treatments. Surface roughness (Sa) for the treated and untreated enamel surfaces of the teeth in all groups were evaluated with a three-dimensional laser scanning microscope after six months.Results: No significant differences were found between HP6 and CP10 groups immediately after whitening (∆E10.6 ± 1.6 vs. 11.4 ± 1.7,p> 0.05) and at six months after treatments (∆E9.0 ± 1.9 vs. 9.2 ± 2.5,p> 0.05), or between HP35 and HP40 groups immediately after whitening (∆E5.9 ± 1.2 vs. 5.3 ± 1.7,p> 0.05) and at six months after treatments (∆E7.2 ± 1.6 vs. 7.7 ± 1.3,p> 0.05). The two at-home whitening systems achieved significantly better whitening outcomes than the two in-office products immediately after whitening (p< 0.05). However, at six months after treatments, the differences between at-home and in-office treatments had narrowed significantly (p> 0.05). There were no statistically significant differences with respect to the Sa values between the treated and untreated surfaces (p> 0.05).Conclusions: Tooth whitening products in the same product category have similar whitening efficacies, despite significant differences in treatment durations (7 vs. 140 h, and 30 min vs. 60 min, respectively). Take-home products achieved better whitening outcomes than in-office products, but they needed 14 to 280 times longer treatment durations.