Aim: To compare the effect of different preventive regimens containing fluoride toothpaste and chlorhexidine mouthwash with or without minimally invasive (MI) varnish on Cariogram parameters of high caries risk patients. Materials and Methods: A total of 66 participants were divided into three groups according to the tested regimen, A1: fluoride toothpaste with chlorhexidine mouthwash, A2: fluoride toothpaste with chlorhexidine mouthwash and MI varnish, or A3: fluoride toothpaste only (control group). All Cariogram parameters were evaluated and recorded according to Cariogram software (Cariogram, Internet Version 2.01, April 2, 2004 Copyright: D. Bratthall, Sweden) at baseline and after 3, 6, and 12 months. Clinical oral examination was carried out for recording caries experience and plaque scores. The salivary profile was generated by recording buffer capacity, salivary flow rate, and mutans streptococci count. Fluoride program was given according to each group, while the remaining parameters were kept constant. Statistical analysis was performed with significance level set at P ≤ 0.005. Results: Regarding Cariogram sectors, the green, red, and light blue sectors showed a statistically significant difference in all groups. The MI varnish group showed the best results followed by the chlorhexidine mouthwash group and finally the control group using fluoride toothpaste only. Conclusion: MI varnish with other preventive measures could be effectively applied to reduce caries risk, especially in high caries risk patients. [ABSTRACT FROM AUTHOR]