Elimination of leukoplakia is one of the strategies for prevention of oral cancer. However, the efficacy of reducing malignant transformation for the treated leukoplakia has rarely been reported despite a number of studies addressing its malignant transformation to oral cancer after intervention. The obstacle to do so is partially due to different lengths of follow-up and partially due to lack of information pertaining to the disease natural history that can be taken as a standard group for comparison. This work aimed to quantify the progression from leukoplakia to carcinoma with and without intervention after systematic literature review. The overall comparison of the efficacy of intervention across studies was therefore made. The literature between 1934 and 2001 was first reviewed, including two studies addressing the disease natural history model and 15 studies pertaining to intervention model in reducing malignant transformation. The simple constant-incidence exponential model and non-constant incidence models (Weibull and Quadratic models) were therefore applied to estimate annual malignant transformation after intervention in various studies. Annual transition rates pertaining to the disease natural history were also estimated by Markov models. Intervention efficacy index using 10-year cumulative incidence from both models was also developed to assess intervention efficacy across studies. For the disease natural history, the estimates of annual transition rate of leukoplakia, annual transition rate from leukoplakia to oral cancer in the PCDP, and annual transition rate from the PCDP to clinical phase were 0.00121 (0.00019-0.00150), 0.0605 (0.0436-0.0755), and 1.8797 (0.13242-2.4352), respectively. Similar findings were observed in another retrospective study. Annual malignant transformation rates after intervention range from 0.0003 to 0.062 assuming constant incidence. Studies assuming non-constant incidence show different patterns of increasing or decreasing risk with time. The estimates regarding the efficacy of intervention for each study with different follow-up periods ranged from 42.9 to 99.3%. The heterogeneity of intervention efficacy due to a wide range of annual rates of malignant transformation was demonstrated in this review. This implies that prevention program for reducing malignant transformation may vary with different areas. Factors need to be considered including different diagnosis criteria, different histological type, distributions of risk factor, different patient resources, and different compliance rates or insufficient medical intervention.