While biologics are highly effective, most psoriasis patients do not achieve complete skin clearance with their biologic monotherapy. How to achieve complete skin clearance in psoriasis patients who fail their biologic is not well characterized. To describe treatment approaches in psoriasis patients who fail to achieve complete clearance from their biologic, we modeled and assessed the efficacy, cost, and safety of three treatment approaches– adding a topical agent with their biologic, escalating the biologic dose, and switching to a different biologic. Efficacy of each approach was obtained from literature identifying complete clearance defined as 100% improvement in Psoriasis Area and Severity Index and/or Physician’s Global Assessment score of clear. Cost of each treatment approach was calculated using medication wholesale acquisition cost obtained from Medi-Span Price Rx. Safety was assessed by adverse event (AE) rates. Complete clearance in patients not cleared on their initial biologic was achieved when adding calcipotriene/betamethasone dipropionate (Cal/BD) foam (28%), switching to guselkumab (20%), and switching to infliximab (15.8%). Adding Cal/BD foam to the initial biologic ($3,780 per additional patient cleared) was a less costly approach compared to the lowest cost dose escalation (guselkumab; $73,370 per additional patient cleared) or switching the initial failed biologic to the lowest cost alternative biologic (infliximab; $88,250 per additional patient cleared). There were no treatment-related or serious AEs when adding Cal/BD foam. Adding a topical agent may be an efficacious, low cost, and safe approach to achieve complete clearing in psoriasis patients who previously failed to clear on their biologic. J Drugs Dermatol. 2020;19(2)188-194. doi:10.36849/JDD.2020.3989