Treatment of moderate to severe psoriasis often requires systemic therapy, including biologics. Partial response to biologics and relapses are commonly managed with dose escalation. Secukinumab is a relatively new biologic that is currently used to treat moderate to severe psoriasis. There has been no literature published on dose escalation of secukinumab. This article describes the off-label use of a higher dose of secukinumab (450 mg every 4 weeks) instead of the standard dosing (300 mg every 4 weeks) in 2 patients with moderate to severe psoriasis. The first case involves a male patient with a high body mass index (BMI) (≥30 kg/m2) and severe psoriasis who was started on secukinumab at 450 mg following a partial response to treatment with the standard 300-mg dose. His psoriasis significantly improved with the higher dose of secukinumab. The second case discusses a female patient with treatment-resistant psoriasis and a BMI of 31.6 kg/m2 who initially achieved a complete remission with standard dosing of secukinumab. Later, her psoriasis relapsed and she was dose-escalated to secukinumab 450 mg in an attempt to recapture response, but this dose escalation was unsuccessful. In both cases, there were no adverse events observed with a higher dose of secukinumab. These cases demonstrate that dose escalation of secukinumab (450 mg rather than on-label 300 mg every 4 weeks) may be considered in selected patients with incomplete clearance, particularly for those with a high BMI. However, secukinumab dose escalation may not be as beneficial in patients with loss of efficacy.