This post hoc analysis assessed baseline CRP impact on efficacy/patient-reported outcomes (PROs)/safety of tofacitinib in ankylosing spondylitis (AS). Phase 2/Phase 3 data from patients with active AS were used. Endpoints (weeks 12/16/48) including Assessment of SpondyloArthritis International Society 20%/40% improvement (ASAS20/ASAS40), AS Disease Activity Score (ASDAS)-CRP low disease activity (ASDAS-CRP LDA), 50% improvement in Bath AS Disease Activity Index (BASDAI50), and PROs (pain/fatigue) were stratified by baseline CRP (mg/L): <5 (normal)/≥5 (elevated); and <10/≥10. Safety outcomes were evaluated by <5/≥5mg/L. Overall, 372 patients were included (69.6%, ≥5mg/L; 50.8%, ≥10mg/L). At baseline, in the <5mg/L group, more placebo-treated than tofacitinib-treated patients received concomitant non-steroidal anti-inflammatory drugs (NSAIDs)/sulfasalazine. Week 12 efficacy/PRO responses were generally higher for tofacitinib versus placebo, regardless of baseline CRP. The treatment effect (placebo-adjusted response) at week 12 was generally numerically higher in ≥5/≥10 versus <5/<10mg/L groups. Treatment-emergent adverse events (TEAEs) and 'all infections' incidence rates were numerically higher for tofacitinib versus placebo in patients with <5mg/L, but similar for tofacitinib versus placebo in patients with ≥5mg/L. Regardless of baseline CRP, tofacitinib was more efficacious versus placebo (week 12). The placebo-adjusted efficacy/PRO responses were generally numerically higher in patients with ≥5/10mg/L versus <5/10mg/L. The higher concomitant NSAID/sulfasalazine exposure may have improved efficacy responses in the baseline <5mg/L placebo group, and ultimately affected the tofacitinib treatment effect. Safety was consistent with previous studies of tofacitinib in AS, with numerically higher TEAEs and 'all infections' incidence rates for tofacitinib versus placebo in patients with <5mg/L.