Aims: To evaluate the effects of certolizumab treatment on insulin resistance (IR), lipid parameters, and cardiovascular (CV) risk in patients with ankylosing spondylitis (AS). Methods: This prospective study included 80 consecutive patients with AS (52 males, 28 females) and 74 control subjects (48 males, 26 feemales). The AS patients and control group were compared in respect of basal values. All AS patients with active disease were treated with certolizumab. Biochemical profiles were obtained before and after 24 weeks of certolizumab treatment. Homeostatic model assessment-insulin resistance (HOMA-IR) was used to measure IR and the quantitative insulin sensitivity control index (QUICKI) was used to measure insulin sensitivity. The Framingham equation was used to evaluate CV risk factors. Results: A statistically significant increase was determined in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) values after 24 weeks of certolizumab treatment. No statistically significant change was determined in the plasma atherogenic index (PAI) and low-density lipoprotein cholesterol (LDL-C) values. A statistically significant decrease was determined in HOMA-IR and an increase in QUICKI. When the Framingham risk scoring was compared with the baseline values, a statistically significant decrease in risk was found at week 24. Conclusions: Certolizumab therapy was associated with a significant increase in HDL-C, TC, and TG levels without any significant change in PAI and LDL-C, and was determined to increase insulin sensitivity and lower insulin resistance. There was also a significant reduction in SBP and 10-year Framingham risk scores at 24 weeks after the start of certolizumab therapy.