Abstract Ketamine is often used in pain clinics for refractory chronic pain, but its long-term efficacy is poorly reported. The main objective was to assess the long-term effect of ketamine on pain and health variables in patients with refractory chronic pain. A prospective, multicenter, 1-year follow-up observational study (NCT03319238) was conducted in 30 French pain clinics where ketamine is commonly prescribed. This study focused on patients with 1 ketamine delivery procedure (n = 256). The primary endpoint was pain intensity (0-10 numerical pain rating scale) before and after ketamine every month for 1 year. Secondary outcomes aimed to identify pain trajectories by semiparametric mixture models and to collect adverse events. The following data were obtained for 256 patients: Pain intensity decreased significantly (6.8 ± 1.8, n = 240 at baseline vs 5.7 ± 1.8, n = 93 at 12 months; P < 0.001). The effect size of the main endpoint was 0.61 (95% confidence interval: [0.40-0.80]; P < 0.001). Three pain trajectories were identified: 16.0% of patients in “mild pain” (mostly neuropathic pain), 35.3% in “moderate pain,” and 45.7% in “severe pain” (mostly fibromyalgia) trajectory. Neuropathic pain and fibromyalgia presented opposite outcomes, pain severity being associated with anxiety, depression, and a poorer quality of life. Adverse events occurred at 1 week in 108/218 [50%] patients, and this rate gradually decreased throughout the follow-up. This real-life study in chronic pain identified distinct pain trajectories and predictive variables of ketamine efficacy. It is now pivotal to further study and optimize the subtyping of patients to provide the most effective and safe ketamine treatment in this vulnerable population.