Abstract Purpose: Organs at risk sparing without compromising adequate coverage to the target volumes is the main challenge during left breast cancer adjuvant radiation therapy. Advanced radiotherapy techniques have been investigated to improve the dose distributions and to reduce toxicities. These techniques includes deep inspiration breath hold, accelerated partial-breast irradiation, Intensity Modulated Radiation Therapy. Supine positioning (SP) is the most commonly used and the standard tangent set-up for breast radiotherapy. Our purpose is to compare the Semi-lateral decubitus position(SLDP) versus SP regarding the dose distribution to the left Chest wall/Whole breast (WB), ipsilateral left axilla, contra-lateral breast, thyroid, spinal cord, ipsilateral lung, heart, LAD (Left Anterior Descending Artery), as well as determining the reproducibility of the Alexandria left breast board-16 (ALB-16) by portal image verification. Methods: We invented a new breast board ALB-16 to induce SLDP allowing tilting the patient towards the right side, elevating the patient's left side at a certain angle adjusted according to the patient’s body surface area and the gantry width of the CT simulator. Simulation process was performed in two different positions whilst the patients were freely breathing, the first scan in SLDP and the second in SP. Fifty women with a left sided breast cancer who underwent either mastectomy or lumpectomy were enrolled in this study for dosimetric comparison between the SLDP and the SP. The mean radiotherapy dose to the CW/WB, axilla, thyroid, left lung, heart, LAD, Spinal cord and the contra-lateral right breast in SLDP and the SP for the same patient were compared. Secondly, analysis was conducted on the fifty patients who were treated in SLDP by ALB-16 in comparison with a control group treated in SP to determine ALB-16 reproducibility. Results: On dosimetric analysis of the two positions, SLDP was found to significantly decrease the mean dose to the heart when compared with SP (2.2Gy vs. 2.9Gy respectively), LAD (5.4Gy vs. 7.2Gy) and the Spinal cord Dmax (7.5Gy vs. 12.6Gy) with a (p<0.01), while maintaining a similar coverage to the axillary lymph nodes levels I, II and III and the SCV group (91.13%, 89.9%, 88.9% and 93.9% vs. 91.3%, 90.2%, 89.5% and 94.1% respectively)(p =0.73, 0.37, 0.29 and 0.67) SLDP improved coverage to the target PTV mean dose (95.2% vs. 94.2%, p<0.01). SLDP decreased the mean dose to the contralateral breast (2.27Gy vs. 2.52Gy, p= 0.08). However, it achieved slightly a higher mean dose to the thyroid gland (79.8Gy vs. 16.8Gy, p= 0.56). The mean dose to the ipsilateral lung was slightly higher than SP (22.5% vs. 20.3%) with a statistically significant difference (p<0.01). For the secondary analysis, setup error in lateral (x) direction was higher in SLDP (0.66cm vs.0.49cm, p=0.028), setup error in vertical (y) direction in SLDP was lower than SP (0.39cm vs. 0.55cm, P=0.013). For the changes in longitudinal direction (Z), there was a slight difference between both positions (0.49cm vs. 0.39cm, p= 0.56). The length of deviation vector (3D vector) was (0.95cm in SLPD vs.0.87 in SP), the mean difference between vector lengths was only (0.08 cm) and this difference wasn’t statistically significant (p= 0.441) indicating the overall reproducibility of the ALB-16 breast board in comparison to standard supine breast board. Conclusions: ALB-16 Breast board is considered a reproducible method of setup for patients receiving left breast cancer adjuvant radiotherapy. It is comparable with the conventional supine breast board in regards of setup errors variability. SLDP spared the heart, LAD and the spinal cord, with a better WB/CW PTV coverage. SLDP can be used in patients whom regional nodal irradiation is indicated while maintaining low contralateral breast dose. Citation Format: Omar Saeed Emam, Mohamed Abouegylah, Rasha Elsaka, Amr Munir, Fady Aziz, Abdelsalam Attia Ismail, Amr Abdelaziz Elsaid. Semi-lateral decubitus position using Alexandria left breast board-16. A prospective study regarding dose distribution and reproduciblity [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-21.