Aim: Based on a maternal observation, we aimed to evaluate the treatment effectiveness of guaiazulene (GA) containing local pomade in the high-risk neonates with recalcitrant diaper dermatitis (RDD). Methods: We included 30 NICU patients of RDD, with level II-III aged between 22 and 67 days. Study group patients (n = 20) were treated with GA containing local pomade (0.05 g/100 g). Control group consisted of patients who had extended antifungal treatment. A visual scale was used to assess the response to treatment at the end of a week. Scoring was done at the beginning of the treatment, on the first, third and seventh days. Results: Statistically significant differences in visual scores were determined between the two groups at the initial and following days of the treatment. In study group, improvements at the first and third days of the treatment were better than those of control group. Additionally, complete recovery rate in study group was better than that in controls. Conclusion: Having beneficial but no adverse effects, GA containing local pomade provided rapid recovery in risky neonates with RDD, who required rapid improvement.