Background: Children are at high risk of drug-related problems, increased risk of treatment failures, and high treatment costs. We aimed to evaluate the effect of pharmacist-led interventions on physicians’ prescribing for pediatric outpatients. Methods: A prospective study with pre- and post-intervention measurement assessment was conducted to collect pediatric outpatients’ prescriptions during the pre-intervention period (January 2020) and post-intervention (August 2020) at a children’s hospital in Vietnam. Drug-related problems were identified and categorized according to Pharmaceutical Care Network Europe (PCNE), version 9.1. The intervention program was developed based on the results of pre-intervention observations. After the intervention, prescriptions were evaluated. Statistical tests were used to compare the proportions of drug-related problems before and after the intervention and to identify factors related to drug-related problems. Results: There were 2788 out of 4218 (66.1%) prescriptions with at least one drug-related problem before the intervention. Of these drug-related problems, the most common was inappropriate timing of administration and incorrect dosage (36.1% and 35.6%, respectively). After the intervention, the percentage of prescriptions with at least one drug-related problem was 45.5% (p < 0.001). Most of the drug-related problem types decreased significantly (p < 0.05). The binary logistic regression analysis results showed that in addition to pharmacists’ intervention, patients’ gender, primary disease, comorbidity status, and the total number of drugs prescribed were also factors related to drug-related problems. Conclusions: Drug-related problems in pediatric outpatients were quite common. Pharmacists’ intervention helped to improve the prevalence and types of drug-related problems.