Radiofrequency (RF) microneedling produces patient discomfort which deters patients from completing the recommended treatment series. The primary objective was to determine the tolerability, safety, and efficacy of a neurocosmetic postprocedure cream post-RF microneedling in reducing patient discomfort and enhancing recovery across the length of the study and, secondarily, to evaluate against a leading comparator. The third objective was to evaluate the efficacy of the neurocosmetic on self-perceived improvement and objective grading. An Institutional Review Board (IRB) approved, fourteen-day, randomized, single-center, double-blind, controlled clinical case study was conducted with 11 healthy female subjects, 6 randomized to the neurocosmetic and 5 to the comparator cell. Following a 7-day washout period, subjects received RF microneedling (face and neck) and applied the postprocedure cream twice daily for 7 days. Objective and subjective tolerability, self-assessments, and clinical photography were performed immediately postprocedure, 24 h, three and seven days following the procedure. The neurocosmetic was tolerable and safe. Erythema and stinging immediately decreased postprocedure, postneurocosmetic application. After 24 h, 83% favorably agreed the neurocosmetic "reduced irritation on the skin post-procedure," and after 7 days, 100% favorably agreed "experience with the product was positive and I would be interested in returning for a second treatment." The neurocosmetic reduced skin tone redness in the face and neck faster and to a greater degree when measured against a comparator. The neurocosmetic postprocedure cream improved patient discomfort and enhanced recovery when used immediately post-RF microneedling and after 7 days. Pro00064211.