Abstract: Introduction: In one author’s experience, ampicillin is an effective alternative antibiotic for acne; however, current literature for ampicillin use in acne is scant. The objective of this study was to demonstrate the response of oral Ampicillin in acne.Methods: A retrospective analysis of 243 patients with Acne vulgaris treated with Ampicillin 500mg twice daily was conducted. The severity of acne (on a scale of 0 to 3) at the last visit was compared with baseline severity determined at the initial visit. Results were analyzed using the paired samples t-test. Results: The average severity of acne was reduced from 1.54 to 0.90 (p < 0.001). The average severity was reduced from 1.69 to 1.09 (p < 0.001) among men, and from 1.48 to 0.84 (p < 0.001) among woman. Lastly, average severity was decreased from 1.67 to 1.12 (p < 0.001) in patients with nodulocystic acne, from 1.45 to 0.77 (p < 0.001) with inflammatory acne patients, and from 1.00 to 0.38 (p < 0.001) in patients with comedonal acne. Limitations: This study was limited by its retrospective nature and analysis of a small patient population. Additionally, a validated acne scoring system was not used due to provider documentation. Conclusion: To conclude, Ampicillin had a positive effect on our patient’s acne.