Background: Anesthesia information management systems (AIMSs) automatically import real-time vital signs from physiological monitors to anesthetic records, replacing part of anesthetists' traditional manual record keeping. However, only a handful of studies have examined the effects of AIMSs on anesthetists' monitoring performance. Objective: This study aimed to compare the effects of AIMS use and manual record keeping on anesthetists' monitoring performance, using a full-scale high-fidelity simulation. Methods: This simulation study was a randomized controlled trial with a parallel group design that compared the effects of two record-keeping methods (AIMS vs manual) on anesthetists' monitoring performance. Twenty anesthetists at a tertiary hospital in Hong Kong were randomly assigned to either the AIMS or manual condition, and they participated in a 45-minute scenario in a high-fidelity simulation environment. Participants took over a case involving general anesthesia for below-knee amputation surgery and performed record keeping. The three primary outcomes were participants' (1) vigilance detection accuracy (%), (2) situation awareness accuracy (%), and (3) subjective mental workload (0-100). Results: With regard to the primary outcomes, there was no significant difference in participants' vigilance detection accuracy (AIMS, 56.7% vs manual, 56.7%; P=.50), and subjective mental workload was significantly lower in the AIMS condition than in the manual condition (AIMS, 34.2 vs manual, 46.7; P=.02). However, the result for situation awareness accuracy was inconclusive as the study did not have enough power to detect a difference between the two conditions. Conclusions: Our findings suggest that it is promising for AIMS use to become a mainstay of anesthesia record keeping. AIMSs are effective in reducing anesthetists'workload and improving the quality of their anesthetic record keeping, without compromising vigilance.