Meaning in Life (MiL) is considered protective against suicidal behavior (SB). However, few studies specifically addressed the role of the constructs, "presence of MiL" and "search for MiL," and their dynamic interplay. In this cross-sectional study of patients with SB (N = 199) visiting a psychiatric Emergency Department for either suicidal ideation (SI) or suicide attempt (SA), we pursued the following objectives: 1) to explore the relationship between the two constructs; 2) to verify the protective value of presence of MiL on SB; and 3) to assess the influence of search for MiL on the relationship between presence of MiL and SI. The two constructs were found to be independent of one another. Higher presence of MiL was globally associated with lower SB levels, particularly SI. Search for MiL was not related to SB and did not moderate the relationship between presence of MiL and SI. In conclusion, formal support for the role of presence of MiL against SB in a psychiatric sample was demonstrated. These findings, with a view toward refinement of SB risk assessment and new psychotherapeutic approaches, may lead to an enrichment of the dialogue with suicidal patients to help alleviate their unbearable suffering. Our conclusions must be replicated in psychiatric clinical populations in settings other than a psychiatric ED and by using a longitudinal prospective and case-control study design.