Background Fixed combination calcipotriol 50 μg/g (Cal) plus betamethasone 0.5 mg/g (BD) foam has been developed as a new treatment option for patients with psoriasis. Methods The randomized, parallel‐group, investigator‐blinded Phase III, 12‐week PSO‐ABLE study compared the efficacy and safety of Cal/BD foam with Cal/BD gel. Patients aged ≥18 years with mild‐to‐severe psoriasis were randomized 4:4:1:1 to once‐daily Cal/BD foam, Cal/BD gel, foam vehicle or gel vehicle (NCT02132936). The primary efficacy endpoint was the proportion of patients who were clear/almost clear with a ≥ 2 grade improvement according to the physician's global assessment of disease severity (i.e. treatment success) at week 4 for Cal/BD foam vs. week 8 for Cal/BD gel. Secondary efficacy endpoints included: proportion of patients achieving at least a 75% reduction in modified psoriasis area and severity index (mPASI75), and time to treatment success (TTTS). Safety was monitored throughout. Results A total of 463 patients were randomized: Cal/BD foam (n = 185), Cal/BD gel (n = 188), foam vehicle (n = 47), gel vehicle (n = 43); overall completion rate was 90%. Cal/BD foam achieved higher treatment success rates (38% vs. 22%; P < 0.001) and mPASI75 (52% vs. 35%; P < 0.001) by week 4 than Cal/BD gel by week 8. Median TTTS with Cal/BD foam was 6 weeks; this could not be determined for Cal/BD gel as 50% treatment success was not achieved (P < 0.001). Adverse drug reactions were reported in 14 (7.6%) Cal/BD aerosol foam patients and 7 (3.7%) Cal/BD gel patients; all were single events except for itch with Cal/BD aerosol foam (n = 5; 2.7%) and worsening psoriasis with Cal/BD gel (n = 3; 1.6%). Conclusion Cal/BD aerosol foam showed significantly greater efficacy after 4 weeks, than 8 weeks of treatment with Cal/BD gel, with similar tolerability.