Health Information Technology (HIT) integration is one of the pillars of healthcare modernization in the Kingdom of Saudi Arabia, but there is a paucity of empirical data quantifying its particular effect, as well as the centrality of medical secretaries, on patient safety outcomes. The purpose of this study was hence to determine the independent and combined effect of HIT implementation and medical secretarial and medical records efficacy on patient safety in Saudi hospitals. It is a quantitative research, correlational study that was carried out in three hospitals located in Riyadh, which are tertiary care. A validated scale was used to collect the data on HIT implementation, medical secretarial and medical records efficacy, and patient safety culture in 289 healthcare professionals (physicians, nurses, and medical secretaries). Hierarchical regression analysis in the presence of experience and hospital demonstrated that the joint predictors produced 76 percent of the variance on patient safety scores (R 2 = 0.76, F (6, 282) = 149.33, p.001). Both the HIT scores ( 0.59, p < .001) and medical secretarial and medical records scores ( 0.26, p < .001) had significant, positive predictors. Also, mediation analysis revealed strong partial mediation, meaning that HIT also augments patient safety indirectly through the improvement in medical secretarial and medical records efficacy (indirect effect = 0.19, Boot CI [0.12, 0.27]). The evidence from the results is conclusive that strong HIT systems and efficient medical secretarial and medical records assistance are independent, relevant, and synergistic causes of patient safety. This research gives the policy makers and hospital authorities a proven model, that is, there is an urgent need to invest in both technological infrastructure and human resources on the administrative side to ensure improved patient safety within the Saudi health care system.