OBJECTIVE This clinical trial aimed to compare the caries-preventive effect of annual application of 38% silver diamine fluoride solution (SDF) with 5% sodium fluoride varnish (FV) to the anterior primary teeth of children. The hypothesis was that SDF was superior to FV at 1 year. Secondary objectives were to determine the child's cooperation and the parent's satisfaction and assess adverse effects. METHODS We recruited 688 3- to 4-year-old children and randomly allocated them to receive SDF or FV (positive control) on their 6 upper anterior teeth. Tooth-surface status was recorded using the decayed, missing, and filled surfaces index. A trained observer rated the child's cooperation as "totally cooperative" or "not totally cooperative." We used a questionnaire to determine the parent's satisfaction as "satisfied," "neutral," or "dissatisfied." Adverse effects (yes/no) were evaluated 1 day and about 1 year after treatment. RESULTS Of the children, 434 (SDF, n = 209; FV, n = 225) completed the trial. The mean new decayed tooth surfaces developed for SDF and FV groups were 0.4 ± 1.5 and 0.4 ± 1.3, respectively (P = .65). Child's cooperation for SDF and FV therapy was 71% (244/344) and 70% (241/344), respectively (P = .89). Parent's satisfaction for SDF and FV therapy was 71% (148/209) and 69% (155/225), respectively (P = .29). Adverse effects were found neither at 1 day nor at about 1 year after treatment for either treatment arm. CONCLUSIONS SDF is not superior to FV for caries prevention in primary upper anterior teeth at 1-year follow-up. Child's cooperation and parent's satisfaction were similarly high with SDF and FV therapy at 1-year follow-up. Neither short-term nor long-term adverse effects were observed. This study is registered at ClinicalTrials.gov (NCT04399369).