Objective: To compare clinical efficacy and safety of Rembrandt Plus (RP), Rembrandt Plus Enhanced (RPE) and Crest Whitestrips (CWS). Methods: Subjects (84) were randomly assigned to three groups (28/group). Demographics and medical history were collected, and subjects were examined for oral tissues,tooth shade of maxillary incisors (Bioform Color Ordered Shade Guide, Dentsply International Inc., York, PA), and tooth sensitivity. The application of whiteners was 60-minute for the RP (Den-Mat, Santa Maria, CA) group, 30-minute for the RPE (Den-Mat) group, and 30-minute for the CWS (P&G, Cincinnati, OH) group, each twice daily for 14 days. Subjects in the RP and RPE groups used Rembrandt Plus Toothpaste (Den-Mat) and the CWS group used Crest Extra Whitening Toothpaste (P&G) during the experiment period. The use of toothpaste alone continued for an additional 11 weeks. Clinical examinations were conducted at 14-day and 3-month. Bioform shade data were analyzed using the One-Way ANOVA and Student-Newman-Keuls methods, while oral tissue and sensitivity results were descriptive. Results: The average baseline Bioform shade values (12.32, 13.09 and 11.50) were comparable among the three groups. The shade reductions after 14-day treatments were -7.85, -9.35 and -6.98 for the RP, RPE and CWS, respectively. The difference between the RPE and CWS was significant (p=0.009). The 14-day incidence of sensitivity was 26.9%, 19.2% and 35.7% for the RP, RPE and CWS groups, respectively. No significant clinical evidence of other adverse effects on oral tissues was detected. Further significant shade reduction was observed in the RP (-0.75) and RPE (-0.70) groups at 3 month, while it remained essentially the same in the CWS group (+0.08). Conclusion: All three at-home whitening systems are effective and safe, with Rembrandt Plus Enhanced being the most effective among the three systems tested. Support by Den-Mat Corporation.