Electronic health record (EHR) systems have become a basic need in most health care facilities worldwide. However, little can be said about the developing nations’ use of it. Nevertheless, Ghana is one of the very few countries in Africa to start using EHRs. Nursing is a field that has been substantially influenced by the use of hospital electronic information management systems (HEIMS). More importantly, the successful implementation of any mHealth and EHRs critically depends on user acceptance. Therefore, as nurses in Ghana work at the frontline of the health care system in the country with access to vital records about the patients, it is important to assess what motivates them to use the system. This study applied a non-experimental survey design. An electronic platform questionnaire on smartphones was used to collect data on 660 nurses. Statistically, AMOS structural equation modeling (SEM) was employed to examine the research model. “Behavioral intention” (BI) to HEIMS use was significantly predicted by effort expectancy (EE) ( p <.001). Notably, EE had an effect on BI, which explains the 37% variance in the intention of nurses to use HEIMS. Likewise, use behavior (UB) of HEIMS was also significantly predicted by performance expectancy (PE) ( R2 = .25), EE ( R2 = .311), and BI ( R2 = .397), and all explained 46% of the variance in nurses’ acceptance of HEIMS. Nurses’ acceptance of HEIMS was significantly predicted by PE, EE, and BI. Based on these findings, hospital administrators should put measures in place that will boost the nurses’ confidence in using HEIMS as well as endeavor to adopt and implement a very user-friendly system.