Aim: Postoperative coverage of periodontal surgery sites can help protect the treated area, facilitate wound healing and decrease postperiodontal surgery pain. The aim of this study was to compare the cytotoxic and clinical efficacy of two periodontal dressings after periodontal flap surgery. Materials and methods: In this study 23 patients requiring modified Widman flap in at least two quadrants in the same arch were selected; one quadrant was dressed with Reso-pac, and the other was dressed with Coe-pak. The clinical efficacy of these two dressings was evaluated by comparing plaque, granulation tissue formation, pain, bleeding on probing, and color of gingiva. To compare their cytotoxicity, human gingival fibroblast were exposed to 1- and 3-day extracts of the dressings and MTT test was used to measure cell viability after 24 and 48 hours. Cell apoptosis and necrosis were evaluated by flow cytometric analysis. Data were analyzed by Chi-square and independent t-test and SPSS 20 Software. Results: Plaque and granulation tissue formation rates were significantly lower in Reso-pac covered sites compared to coe-pak (p value < 0.001). Other variables including pain, bleeding and gingival color did not show any significant differences (p value 0.05). V iable fi broblast c ells w ere h igher f or R eso-pac compared to Coe-pak (p < 0.05). A higher percentage of necrotic cells in the day one Coe-pak extract group after 24 and 48 hours were observed compared to Reso-pac (6.23 and 4.97 vs. 2.71 and 2.76%). Conclusion: According to our results, Reso-pac is as effective as Coe-pack. It also has further positive effects of less plaque accumulation and granulation tissue formation and is more biocompatible for HGF cells with less cytotoxic effects on cells in the first days after surgery. Clinical significance: Reso-pac may be considered as a dressing of choice in periodontal surgeries with less plaque accumulation and granulation tissue formation plus better biocompatibility and ease of application compared to Coe-pak.