Background. Contrast medium (CM) administration during computed tomography (CT) enhances the accuracy in the detection and interpretation of abnormalities. Evidence from literature also validate the essence of CM in imaging studies. CT, by virtue of its ubiquity, ease of use, speed, and lower financial footprint, is usually the first investigation in cases of headache. Through a multicenter retrospective analysis, we compared findings of contrast-enhanced CT (CECT) to noncontrast-enhanced CT (NCECT) head examinations among patients presenting with headache. Methods. A multicenter retrospective analysis of four years’ CT head examination data at two radiology centers located in Central and Western Regions of Ghana were reviewed. Records of patients who presented with headache as principal complaint between January 2017 and December 2020 were reviewed. A total of 477 records of patients with headache were identified, retrieved and evaluated. A Chi-square test and Fisher exact test were used to compare the CECT and NCECT groups. Binary logistic regression analysis was computed to assess association between CECT and each CT findings. Statistical significance was considered at
p
<
0.05
with a 95% confidence interval. Results. A significant proportion of the patients was females (51.8% in CECT and 60% in NCECT). The NCECT group (40.06 ± 14.76 years) was relatively older than the CECT group (38.43 ± 17.64 years). There was a significant difference between the CECT and NCECT in terms of age (
p
=
0.002
) and facility CT was performed (
p
<
0.0001
). The rate of abnormalities was higher in CECT (43.5%, 166/382) compared NCECT (37.9%, 36/95). There was no significant association between CT head findings and contrast enhancement. Conclusion. CECT examination accounted for 5.6% increase in the detection of head abnormalities. Efforts required to establish local standard operation procedures (SOPs) for contrast medium use especially in CT head examinations. Further studies to improve the knowledge of agents, mechanism of action, and safety of contrast media used among practitioners in Ghana is recommended.