Objective Hopelessness is a proximal risk factor of suicide. Meaning in life has been found to be a protective factor against suicidal ideation; however, the majority of studies that have explored the role of meaning in life in the context of suicidality have been conducted in nonclinical populations. The aim of this study was to investigate whether meaning in life can moderate and buffer the association between suicide risk factors and hopelessness in a clinical sample with a heightened risk of suicide. Method A total of 224 participants diagnosed with mental disorders completed self‐report measures of suicide risk factors, hopelessness, and meaning in life. Results The main result from this study was that meaning in life moderated the association between suicide risk factors and hopelessness. Conclusion Meaning in life is an important variable in the prevention and treatment of people at risk of suicide.