Background: Infantile Tremor Syndrome (ITS) is characterized by coarse tremors, anemia, and developmental regression, commonly associated with vitamin B12 deficiency. Current pharmacological management lacks evidence-based guidance for tremor control. This study compared the efficacy and safety of propranolol versus phenobarbitone in managing ITS associated tremors. Methods: We conducted a prospective, randomized, double-blind, controlled trial at a tertiary pediatric center from May 2023 to April 2025. Children aged 6-24 months with clinically diagnosed ITS and moderate-to severe tremors were randomized 1:1 to receive propranolol (1-4 mg/kg/day) or phenobarbitone (3-5 mg/kg/day). The primary outcome was ≥50% tremor reduction at 2 weeks. Secondary outcomes included time to tremor resolution, functional improvements, and safety measures. Results: Twenty-five children were randomized (13 propranolol, 12 phenobarbitone); 24 completed the study. The primary outcome was achieved by 76.9% (10/13) of propranolol-treated participants versus 41.7% (5/12) of phenobarbitone-treated participants (Risk Ratio 1.85, 95% CI: 0.89-3.84, p=0.095; NNT=2.8). Median time to complete tremor resolution showed a trend favoring propranolol (12 vs. 18 days, p=0.067). Propranolol demonstrated significantly greater tremor severity reduction at day 14 (2.7 ± 0.8 vs. 1.9 ± 0.9 points, p=0.028). Both medications had comparable safety profiles. Sustained tremor control at 3-month follow-up was maintained in 90% versus 80% of initial responders. Conclusion: Propranolol shows promising efficacy compared to phenobarbitone for managing ITS-associated tremors, with trends toward faster onset and greater tremor reduction. While statistical significance was limited by the small sample size, the clinically meaningful differences support propranolol as a preferred treatment option for ITS-associated tremors.