Abstract Background Lateral elbow pain (LEP) or lateral epicondylitis (LE) is a common problem affecting both males and females. Multiple therapeutic modalities are used with different outcomes. Objective The current study aimed at description of the effectiveness of a newly introduced modality, Perineural Injection (PNI) therapy in comparison to the already used therapeutic ultrasound (TUS) as a conventional modality in the treatment of resistant LEP (LE). Patients and methods This is a longitudinal interventional study. Thirty patients of both sexes aged between 21 to 62 years old who had LE were randomly allocated into two groups (15 each). In PNI group, 5% buffered dextrose was injected subcutaneously around the lateral epicondyle once weekly for 8 weeks. In TUS group, continuous US was used 3 sessions per week for 4 weeks. Tenderness grading scale, visual analogue scale (VAS), Patient- Rated Tennis Elbow Evaluation Questionnaire (PRTEE) score, and ultrasonographic evaluation were used before and 12 weeks after treatment. Results In both groups, there was a high significant clinical improvement at 12th week after treatment. However, the improvement was better in the PNI group than the TUS group. By US evaluation at 12th week after treatment, there was a significant decrease in hypoechoic areas and disturbed fibrillar pattern in PNI group compared to before therapy (p < 0.001 and = 0.025) respectively. But in TUS group, there was decrease in hypoechoic areas and tendon thickness compared to before treatment (p = 0.02 and 0.026) respectively. Conclusion Both PNI and TUS therapies for LE gave clinical improvement for pain, functional limitations and some ultrasonographic findings (as echogenity, fibrillar pattern and tendon thickness). However, PNI therapy gave better outcome as compared to TUS.