BACKGROUND: The main objective of conservative dentistry is maintaining the health of the dentition and restored teeth free from dental caries. The prevention of dental caries can be achieved by personal prevention programs at home, dental health care professional, and public health application programs. Based on knowledge related to the etiology and pathogenesis of dental caries, this provides a chance for application of effective prevention program for the prevention of dental caries. AIM: This study aimed to evaluate the effect of different preventive regimens using different toothpastes on caries risk using cariogram and decayed, missing, and filled (DMF) scores of high caries risk patients. MATERIALS AND METHODS: The study was conducted on 66 participants with high caries risk. Participants were divided into three groups, 22 participant each. According to the test regimen, where (A1) participants were exposed to a regimen including dual zinc plus arginine-based toothpaste (Colgate total), (A2) participants were exposed to a regimen including zinc-based toothpaste (Crest complete), and (A3) control group was participants that were exposed to a regimen including fluoride-based toothpaste (Signal). The study was carried for 1 year, assessment of cariogram and DMF scores was done in four intervals: T0: baseline, T3: after 3 months, T6: after 6 months, and T12: after 12 months. RESULTS: According to cariogram, there was a statistically significant difference between Groups A1, A2, and A3, where p < 0.001. However, DMF scores of all groups showed no statistically significant difference between the three groups. CONCLUSIONS: Dual zinc plus arginine-based toothpaste is a superior caries preventive regimen in high caries risk patients. CLINICAL SIGNIFICANCE: The benefits of preventive regimen to the practitioner will be providing a non-invasive, and cost-efficient method to prevent dental caries. Benefits to the patient will be an improvement of oral hygiene, prevention of dental caries, and maintain healthy dental supporting structures.