The adoption of health information systems provides many potential healthcare benefits. The government of the Kingdom of Saudi Arabia has subsidized this field. However, like those of other less developed countries, organizations in the Kingdom of Saudi Arabia struggle to secure their health information systems. This issue may stem from a lack of awareness regarding information security. To date, most related studies have not considered all of the factors affecting information security compliance behavior (ISCB), which include psychological traits, cultural and religious beliefs, and legal concerns. This paper aims to investigate the usefulness of a theory-based model and determine the predictors of ISCB among healthcare workers at government hospitals in the Kingdom of Saudi Arabia. The study investigated 433 health workers in Arar, the capital of the Northern Borders Province in the Kingdom of Saudi Arabia. Two phases involved in this study were the hypothetical model formulation and identification of ISCB predictors. The results suggest that moderating and non-common factors (e.g., religion and morality) impact ISCB, while demographic characteristics (e.g., age, marital status, and work experience) do not. All published instruments and theories were embedded to determine the most acceptable theories for Saudi culture. The theory-based model of ISCB establishes the main domains of theory for this study, which were religion/morality, self-efficacy, legal/punishment, personality traits, cost of compliance/noncompliance, subjective norms, information security policy, general information security, and technology awareness. Predictors of ISCB indicate that general information security, followed by self-efficacy and religion/morality, is the most influential factor on ISCB among healthcare workers in the Kingdom of Saudi Arabia. This study is considered as the first to present the symmetry between theory and actual descriptive results, which were not investigated before.