OBJECTIVES: No direct comparisons have been made between infliximab and ustekinumab in the treatment of moderate to severe psoriasis.  A mixed treatment comparative (MTC) meta-analysis was conducted to compare the relative efficacy of infliximab and ustekinumab for the treatment of moderate to severe plague psoriasis.    METHODS: Randomized clinical trials that included infliximab, 5 mg/kg, ustekinumab 45 mg or ustekinumab 90 mg in the treatment arm and reported PASI 75 and PASI 90 endpoints were identified from a systematic literature search. The log odds ratio (log OR) was used as the treatment effect measure using both fixed-effects and random-effects MTC models.  Six trials meeting the inclusion criteria were included in the mixed treatment networks to estimate relative efficacy. RESULTS: The pooled odds ratio of achieving PASI 75 was 164.4 (95% (CI): 78.3 – 330.1) for infliximab, 77.9 (95% CI: 49.3 - 121.1) for ustekinumab 90 mg and 59.8 (95% CI: 37.9 - 92.3) for ustekinumab 45 mg compared to placebo. Pairwise comparison suggested that infliximab is significantly better than and ustekinumab 45 mg to achieve PASI 75 (p <0.05). Pooled odds ratio of achieving PASI 90 was 172.6 (95% CI: 46.7 - 525.2) for infliximab, 79.6 (95% CI: 39.2 - 155.2) for ustekinumab 90 mg and 65.5 (95% CI: (32.1 - 127.8) for ustekinumab 45 mg. Similarly, there was a statistically significant difference between infliximab and ustekinumab 45 mg in attaining PASI 90. Results from random effect models were consistent with fixed effect models.  CONCLUSIONS: Based on this network meta-analysis, a significantly greater proportion of patients with plaque psoriasis are expected to achieve a PASI 75 or PASI 90 response when treated with infliximab 5 mg/kg than with ustekinumab 45 mg or ustekinumab 90 mg.