Background Long-term conditions often coexist with depression and anxiety. Aims To assess the effectiveness of stepped-care psychological therapies for patients with long-term conditions. Method Data from 28 498 patients were analysed using regression to model depression (Patient Health Questionnaire (PHQ-9)) and anxiety (Generalised Anxiety Disorder scale (GAD-7)) outcomes. Post-treatment symptoms and effect sizes ( d ) were estimated for individuals with and without long-term conditions, controlling for covariates. The likelihood of access and response to intensive psychological interventions was also examined. Results Higher post-treatment symptoms were predicted for patients with musculoskeletal problems ( d = 0.22–0.27), chronic obstructive pulmonary disease ( d = 0.26–0.33), diabetes ( d = 0.05–0.13) and psychotic disorders ( d = 0.50–0.58). Most long-term conditions were associated with greater odds of accessing high-intensity therapies, yet individuals who accessed these continued to have higher average post-treatment symptoms. Conclusions Some long-term conditions are associated with greater intensity of care and poorer outcomes after therapy.