Pulp canal calcification is a dental condition that is characterized by the deposition of mineralized tissue within the dental pulp space. While it is primarily a local phenomenon, recent studies have suggested a potential link between pulp calcification and systemic diseases. This study aimed to determine the correlation between certain systemic diseases, medications, and the presence of pulp canal calcification. Second, it aimed to estimate the prevalence of pulp calcification in the smoker population.A pair-matched case-control observational study was conducted from June 2022 to June 2023 at the Faculty of Dentistry, King Abdulaziz University. Digital periapical and bitewing radiographs were used for case-based sampling. Patients were categorized into two study groups: the cases group (n=100), consisting of patients with pulp canal calcification including either pulp stone, pulp canal obliteration, or both. Whereas the control group (n=100), consisted of patients without pulp canal calcification. Detailed medical histories were obtained to identify the presence of systemic diseases. Additionally, systemic medications and smoking status were documented.The participants were divided into two groups; cases (n=100), diagnosed with teeth calcifications and confirmed by radiographic examination, and controls (n=100), showing no evidence of teeth calcifications. Among the patients in the calcification group, 26% had a history of systemic disease compared to 17% in the control non-calcification group with no significant difference between both groups. No correlation between certain medications and pulp canal calcification. Smoking did not demonstrate a statistically significant association with teeth calcifications (p > 0.05).Pulp calcification on routine radiographic examination could indicate an underlying unnoticed systemic disorder that demands accurate referral and subsequent therapy.