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Background: The worldwide human resource gap in anesthesia services often presents a barrier to accessing life-saving and life-improving surgeries. This paper assessed the impact of a ketamine anesthesia package, Every Second Matters-Ketamine (ESM-Ketamine)™, for use in emergency and life-improving surgeries by non-anesthetist clinicians in a resource-limited setting when no anesthetist was available. Methods: We analyzed prospectively collected data from 193 surgeries constituting a pilot implementation of the ESM-Ketamine package, among three sub-district hospitals in Western Kenya. The study population comprises patients who required emergency or life-improving surgery when no anesthetist was available. Non-anesthetist clinicians in three sub-district hospitals underwent a 5-day training course in ESM-Ketamine complemented by checklists and an ESM-Ketamine Kit. Data were collected prospectively every time the ESM-Ketamine pathway was invoked. The training cases, although primarily tubal ligations, were included. The primary outcome measures centered on capturing the ability to safely support emergency and life-improving surgeries, when no anesthetist was available, through invoking the ESM-Ketamine pathway. The registry was critically examined using standard descriptive and frequency analysis. Results: 193 surgical procedures were supported using the ESM-Ketamine package by five ESM-Ketamine trained providers. Brief (<30 s) patient desaturation below 92 % and hallucinations occurred in 16 out of 186 (8.6 %) and 23 out of 190 patients (12.1 %), respectively. There were no reported major adverse events such as death, prolonged desaturations (over 30 s), or injury resulting from ketamine use. Conclusion: This study provides promising initial evidence that the ESM-Ketamine package can support emergency and life-improving surgeries in resource-limited settings when no anesthetist is available. [ABSTRACT FROM AUTHOR]