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Background: Surgical safety has advanced rapidly with evidence of improved patient outcomes through structural and process interventions. However, knowledge of how to apply these interventions successfully and sustainably at scale is often lacking. The 2019 Global Ministerial Patient Safety Summit called for a focus on implementation strategies to maintain momentum in patient safety improvements, especially in low- and middle-income settings. This study uses an implementation framework, knowledge to action, to examine a model of nationwide World Health Organization (WHO) Surgical Safety Checklist implementation in Cameroon. Cameroon is a lower-middle-income country, and based on data from high- and low-income countries, we hypothesized that more than 50% of participants would be using the checklist (penetration) in the correct manner (fidelity) 4 months postintervention., Methods: A collaboration of 3 stakeholders (Ministry of Health, academic institution, and nongovernmental organization) used a prospective observational design. Based on knowledge to action, there were 3 phases to the study implementation: problem identification (lack of routine checklist use in Cameroonian hospitals), multifaceted implementation strategy (3-day multidisciplinary training course, coaching, facilitated leadership engagement, and support networks), and outcome evaluation 4 months postintervention. Validated implementation outcomes were assessed. Primary outcomes were checklist use (penetration) and fidelity; secondary outcomes were perioperative teams' reactions, learning and behavior change; and tertiary outcomes were perioperative teams' acceptability of the checklist., Results: Three hundred and fifty-one operating room staff members from 25 hospitals received training. Median time to evaluation was 4.5 months (interquartile range [IQR]: 4.5-5.5, range 3-7); checklist use (penetration) increased from 20% (95% confidence interval [CI], 16-25) to 56% (95% CI, 49-63); fidelity for adherence to 6 basic safety processes was high: verification of patient identification was 91% (95% CI, 87-95); risk assessment for difficult intubation was 79% (95% CI, 73-85): risk assessment for blood loss was 88% (95% CI, 83-93) use of pulse oximetry was 93% (95% CI, 90-97); antibiotic administration was 95% (95% CI, 91-98); surgical counting was 89% (95% CI, 84-93); and fidelity for nontechnical skills measured by the WHO Behaviorally Anchored Rating Scale was 4.5 of 7 (95% CI, 3.5-5.4). Median scores for all secondary outcomes were 10/10, and 7 acceptability measures were consistently more than 70%., Conclusions: This study shows that a multifaceted implementation strategy is associated with successful checklist implementation in a lower-middle-income country such as Cameroon, and suggests that a theoretical framework can be used to practically drive nationwide scale-up of checklist use.