Antibiotics remain one of the main treatment alternatives in mild-to-moderate hidradenitis suppurativa. The use of topical 15% resorcinol reduces antibiotic pressure and the generation of resistance. However, knowledge on its efficacy and safety is limited. This single-center, prospective, follow-up cohort study evaluated topical 15% resorcinol every 12-h response at 16 weeks. Those individuals with mild-to-moderate hidradenitis suppurativa (Hurley I–II) who started treatment with topical resorcinol monotherapy between April 2019 and May 2020 were eligible for follow-up. The primary endpoint for effectiveness was the proportion of patients who achieved an overall clinical response (complete or partial response) at week 16, evaluated as intention-to-treat. Responses were measured according to the Hidradenitis Suppurativa Clinical Response index. Target lesion size was measured clinically and by ultrasonography. Quality of life was assessed through the Dermatology Life Quality Index (DLQI) questionnaire. Safety was measured by recording the adverse events reported during the follow-up period. A total of 32 patients were enrolled (mean age, 40.1 years [95% confidence interval, 35.7–44.4]; women, 20 [62.5%]; Hurley I, 17 [53.1%]). Under the intention-to-treat analysis, 68.8% (n = 22) of the patients achieved a clinical response. A ≥50% reduction in the size of the main lesion was observed in 56.3% of the patients (n = 18). Some 65.6% (n = 21) of the patients had a ≥50% reduction (improvement) in their baseline DLQI score. Fifty percent of patients who completed the follow-up period experienced adverse events, all of which were local, mild, and transient and did not lead to discontinuation of resorcinol. To conclude, in this cohort study, topical 15% resorcinol was shown to be effective for mild-to-moderate hidradenitis suppurativa and to have a positive impact on quality of life with an acceptable safety profile.