Background : The treatment of acne with antibiotics such as tetracycline or erythromycin may enhance the development of bacterial resistance. From the pathogenesis of acne, zinc has been involved in many pathways of both inflammatory and non-inflammatory acne. Zinc amino acid chelated can increase oral bioavailability and reduce the side effects of zinc salt. Currently, there is no study about the efficacy of zinc amino acid chelated in treatment of moderate acne. Objectives : To evaluate efficacy of zinc amino acid chelated and 0.025% tretinoin cream in moderate acne. Materials and Methods : Seventy patients with moderate acne were enrolled. Each patient was randomized to receive either treatment with oral zinc amino acid chelated or placebo with 0.025% tretinoin cream nightly in both groups. Zinc amino acid chelated (75mg/tab) was given in the dosage of 225mg/day for 3 consecutive months. Clinical improvement was assessed at baseline and at the 4th, 8th and 12th week from the beginning of the study. Overall improvement was assessed by acne count, photographs taken by VISIA, which were evaluated by 3 independent dermatologists. The patient’s satisfactory was assessed by severity of acne, facial oiliness and adverse effects. Result : The mean acne lesion counts of closed comedones, open comedones, papule, pustule and nodule were not statistically difference between zinc amino acid chelated combined with 0.025% tretinoin cream group and placebo combined with 0.025% tretinoin cream group (p>0.05). Similarly overall improvement score and Propionibacterium acnes count demonstrated no difference among two groups. However, the mean serum zinc level in zinc amino acid chelated group was significantly highger than the placebo group. (p<0.05) Gastrointestinal side effects were less reported in patients who received zinc amino acid chelated. Summary: Zinc amino acid chelated and 0.025% tretinoin cream is not superior to placebo with 0.025% tretinoin cream in reducing closed comedones, open comedones, papule, pustule or nodule counts in spite of the significant increasing in serum zinc level.