The goal of lethal means safety (LMS) interventions is to limit the access and/or lethality of specific suicide methods. These interventions purport to reduce or delay suicidal behavior. While most previous systematic reviews have concluded that LMS interventions are likely effective, the included studies primarily utilized observational, quasi-experimental, and/or pre-post study designs, which can be biased and overestimate the impact of interventions. Therefore, the objective of this study was to conduct a systematic review of controlled intervention studies to examine if LMS interventions were associated with reduced suicide deaths and/or attempts in military and civilian populations. Authors searched key databases (PubMed, PsycInfo, CINAHL) from inception to December 2022 for longitudinal study designs with at least one comparator group. Reviewers dually screened articles according to pre-defined eligibility criteria, including articles evaluating the impact of LMS on suicide attempts and/or deaths in a primarily adult (18 to 65 years old) population; specifically, interventions at the individual-, community-, or population-level that were intended to make specific suicide method(s) more difficult to access and/or less lethal were included. Reviewers extracted relevant study characteristics and used the NIH Quality Assessment Tool for Controlled Intervention Studies to assess methodological quality. A total of 7237 studies were screened with 32 articles meeting eligibility for inclusion in the review. Notably, no randomized controlled trials (RCTs) were identified for any intervention, limiting confidence in findings. The majority of the interventions evaluated the impact of population-level firearm legislation on suicide deaths (k = 23). Other interventions examined jumping from bridges (k = 2), carbon monoxide poisoning by barbecue charcoal (k = 3) and motor vehicle exhaust (k = 2), pesticide ingestion (k = 1), and non-specific lethal means assessment (k = 1). Legislation to reduce access to firearms may be associated with fewer suicide deaths relative to populations without the legislation; however, inference at the individual level is not possible. Findings on other LMS interventions were mixed and inconclusive. No studies enrolled a military population. Future studies should utilize a RCT design to elucidate the effectiveness of LMS interventions on suicide deaths and/or attempts at the individual level in specific populations, including active duty military members.