BACKGROUND: Switching between biologics is commonly performed for the management of plaque psoriasis. However, no evidence about switching from secukinumab to ustekinumab has been reported. METHODS: This retrospective observational multicenter study aimed to describe efficacy and safety of ustekinumab in secukinumab nonresponder patients. RESULTS: A total of 21 patients unresponsive to secukinumab were treated with ustekinumab for a mean period of 53.3 weeks. Ustekinumab was effective in reducing disease severity, with significant improvements of both psoriasis area severity index (PASI) and dermatology quality of life index (DLQI) scores. PASI score improvements of 31.8, 44, 77.8, 80.3, 80.5, and 89.6%, at week 4, 12, 24, 36, 48, and above 60 weeks, respectively, were detected (p < 0.05), achieving PASI 50, 75, and > 90 responses in 93.8, 87.5, and 50% of patients at week 48. Four patients withdrew from ustekinumab treatment because of inefficacy, and failure of multiple biologic agents (> 2) seemed to affect ustekinumab drug survival. No serious adverse events (AEs) were reported while 38.1% of patients experienced mild AEs. CONCLUSION: Ustekinumab was safe and effective in treating patients unresponsive to secukinumab.