Background/Objectives: Dental caries continues to represent a major oral health concern in children, particularly in uncooperative patients, where effective sealant placement is often compromised. This study evaluated the long-term clinical performance of hydrophilic (UltraSeal XT hydro) and hydrophobic (Helioseal-F) resin-based sealants in uncooperative children aged 6–9 years, assessing retention and caries incidence over 24 months. Methods: In a split-mouth, double-blinded randomized controlled trial, 34 children (104 first permanent molars) were enrolled, with 31 participants (98 teeth) completing the study. Sealants were randomly assigned to hydrophilic or hydrophobic group, with assessments at 3, 6, 12, 18, and 24 months. Results: Complete retention declined progressively in both groups, from 59.2% to 2.0% in the hydrophilic group and from 42.9% to 0% in the hydrophobic group at 24 months, with no significant intergroup differences (p = 0.719). Caries-free rates decreased from 81.6% to 49.0% in the hydrophilic group and from 75.5% to 40.8% in the hydrophobic group (p = 0.293). Children with definitely negative behavior showed significantly lower retention at 6 and 12 months (p = 0.006 and p < 0.001) compared to those with negative behavior, although differences were not significant at 24 months. Conclusions: Overall, both sealants demonstrated comparable retention and cariostatic performance, indicating that material properties alone do not determine long-term success. Further research should focus on long-term follow-up and comparative evaluation of hydrophilic sealants in cooperative and uncooperative populations to better understand how patient behavior affects sealant performance.