This study was undertaken to appraise the predictive validity of the Visible Occlusal Plaque Index (VOPI) in assessing occlusal caries lesion activity in adolescents. A total of 618 adolescents aged 10 to 15 y were examined at the beginning of the trial and 511 (82.7%) at the 2-y follow-up. Adolescents and parents answered questionnaires about demographics, oral health behavior, and family sociodemographic variables. The VOPI has a 4-point ordinal scale ranging from no plaque to heavy plaque. Molar teeth were assigned to group VOPI 0-1 (no/thin plaque; n = 2,539) and group VOPI 2-3 (thick/heavy plaque; n = 843). At baseline examination, occlusal surfaces at risk of transition (n = 3,382) were either sound (55%), inactive noncavitated lesions (21%), inactive cavitated lesions (1%), active noncavitated lesions (15%), or active cavitated lesions (7%). The relative risk (RR) for caries lesion transition was estimated. Sound occlusal surfaces with no or thin plaque were significantly more likely to remain sound (RR = 1.3; 95% confidence interval [CI]: 1.1-1.4) than those harboring thick or heavy plaque. Inactive noncavitated occlusal lesions presenting no or thin plaque were significantly less likely to progress to active noncavitated lesions (RR = 0.1; CI: 0.0-0.8) than their counterparts with thick or heavy plaque. Active noncavitated lesions harboring thick and heavy plaque had a significantly lowest chance of becoming sound (RR = 0.7; CI: 0.5-0.9) and a highest risk of remaining active (RR = 1.5; CI: 1.1-1.9). Stepwise logistic regression analyses were run according to surface status at baseline and showed that none of the nonclinical predictors were significant for the outcome. The presence of thick and heavy plaque on occlusal surfaces was a predictor for caries lesion development, progression and activity (P < 0.0001). In conclusion, besides being an additional clinical tool for oral hygiene assessment, the VOPI is a predictor for development, progression, and activity of occlusal caries lesion. This is of particular interest for assessment of occlusal lesions undergoing health-promoting transitions.