Background  Ongoing evaluation of biological agents in patients with moderate‐to‐severe psoriasis is needed to support their long‐term use. Objective  To evaluate long‐term efficacy and safety of ustekinumab through 5 years in the PHOENIX 1 study. Methods  Patients were randomized to placebo or ustekinumab (45 mg or 90 mg) at Weeks 0, 4 and every‐12‐weeks thereafter; placebo patients crossed‐over to ustekinumab at Week 12. Clinical response through Week 244 was evaluated using the Psoriasis Area and Severity Index (PASI) in the Overall Population (i.e. patients receiving ≥1 dose of ustekinumab), Initial Responders (i.e. PASI 75 responders Weeks 28/40 re‐randomized at Week 40 to continue every‐12‐week maintenance) and Partial Responders (i.e. <PASI 75 responders adjusted to every‐8‐week maintenance at Weeks 28 or 40). Safety endpoints were evaluated through Week 264 for the Overall Population. Results  Overall, 68.7% (517/753) of ustekinumab‐treated patients completed treatment through Week 244. Initial clinical responses were generally maintained through Week 244 (PASI 75: 63.4% and 72.0%; PASI 90: 39.7% and 49.0%; PASI 100: 21.6% and 26.4%) for patients receiving 45 mg and 90 mg, respectively. Similarly, PASI 75 responses were generally maintained among Initial Responders 79.1% (45 mg) and 80.8% (90 mg) and Partial Responders 57.6% (45 mg) and 55.1% (90 mg). With 3104 patient‐years of follow‐up, rates of overall adverse events (AEs), serious AEs, serious infections, malignancies and major adverse cardiovascular events were generally consistent over time and comparable between doses. Conclusions  Through 5 years of continuous treatment, ustekinumab demonstrated stable clinical response and a safety profile consistent with previous reports.