BACKGROUND Ketoconazole (K), zinc pyrithione (ZP), and salicylic acid (SA) are compounds active in the treatment of dandruff. A thermophobic foam formulation containing K 1%, ZP 0.5%, and SA 2% is now available. STUDY AIM To compare the efficacy of thermo phobic foam with K 2% scalp fluid in the treatment of moderate to severe dandruff. Patients and methods In a randomized, prospective, parallel-group, investigator-blinded, 4-week treatment trial, a total of 54 patients (mean age 43 +/- 8 years) were enrolled. Foam (F group) (n = 37) or K 2% scalp fluid (SF group) (n = 17) was applied daily for 7 days and twice weekly for 3 weeks thereafter. Clinical assessment of the total dandruff severity score (TDSS) was performed at baseline, after 2 and 4 weeks. The TDSS was calculated using a four-grade quantitative score (0 = no dandruff; 3 = severe dandruff) dividing the scalp area into four zones and adding the single score for each area. RESULTS At baseline, TDSS was 7.1 +/- 2 and 5.1 +/- 1 in the F and SF groups, respectively. At the end of treatment period, beneficial effects were observed in both groups. The TDSS was reduced to 2.5 +/- 1 in the F group and to 3.7 +/- 1.2 in the SF group (mean difference in favor of F group: -1.2; 95% CI: -0.57 to -1.8) (P = 0.0003). A complete or nearly complete resolution of dandruff was observed in 24 out of 37 (64%: 95%CI: 48-77%) in the F group and in 7 out of 17 (41%: 95% CI: 21-64%) in the SF group (P = 0.06 between groups). CONCLUSIONS This new antidandruff thermophobic foam has shown to be more effective than ketoconazole 2% scalp fluid in the treatment of severe dandruff.