Isotretinoin (ISO)-associated cheilitis is the most common side effect and the most common reason for discontinuation of ongoing therapy. So, various lip balms are also routinely recommended for all patients. We aimed to investigate the effectiveness of local intradermal injections (mesotherapy) of dexpanthenol into the lips to prevent ISO-associated cheilitis. This pilot study was conducted on patients over the age of 18 using ISO (about 0.5 mg/kg/day). All patients were prescribed only hamamelis virginiana distillate in ointment form as a lip balm. In the mesotherapy group (n=28), 0.1 ml of dexpanthenol was injected into each lip tubercle (4 points total) to the submucosal level. The patients in the control group (n=26) used only the ointment. "ISO cheilitis grading scale (ICGS)" was used in the evaluation of ISO-associated cheilitis. The patients were followed for 2 months. Although there was an increase in ICGS scores in the mesotherapy group compared to the baseline, no statistically significant change was observed after treatment (p=0.545). However, in the control group, there was a statistically significant increase in ICGS scores in the 1st and 2nd months compared to the baseline (p<0.001). Lip balms were needed significantly less frequently in the mesotherapy group compared to the control, both in the 1st and 2nd months (p=0.006, p=0.045; respectively). Lip mesotherapy with dexpanthenol will be a useful option for preventing ISO-associated cheilitis because of its easy application, cost-effectiveness, low complication risk, and high patient satisfaction.