Aim: To investigate the effect of oral valacyclovir on inter-appointment endodontic pain in single-rooted necrotic teeth diagnosed with symptomatic apical periodontitis (SAP).

Materials and Methods: This study was a randomized, triple-blind, placebo-controlled clinical trial conducted on 38 teeth. Participants were assigned to intervention or control groups using stratified randomization based on gender and baseline pain severity. Both groups received similar root canal treatment; the only difference was the administration of valacyclovir in the intervention group and placebo in the control group. Patients' pain levels were monitored and recorded at 6, 24, and 48 hours post-treatment using a Visual Analog Scale (VAS), along with their consumption of analgesic (ibuprofen).

Inclusion Criteria:

• Patients between 18 and 60 years of age
• Require primary root canal treatment (RCT) in single-rooted maxillary or mandibular teeth (anterior or posterior)
• Diagnosed with symptomatic apical periodontitis (SAP) with confirmed pulp necrosis

Exclusion Criteria:

• Teeth with unrestorable crowns
• Presence of endodontic-periodontal or pure endodontic lesions
• Complex root canal anatomies as defined by the AAE Endodontic Case Difficulty Assessment Form
• Internal or external root resorption
• Calcified canals
• Root canal configuration other than Vertucci's Type I
• Pain originating from more than one tooth
• Marginal periodontitis
• Parafunctional habits
• Systemic diseases classified as ASA class II or higher
• Diagnosed migraine or other headache disorders mimicking orofacial pain
• Intellectual or cognitive impairments
• Pregnancy or breastfeeding
• Use of medications affecting pain perception
• Current use of antibiotics or antiviral agents
• Known allergies to study medications