Background: Surgical site infection (SSI) is a common complication after abdominal operation which may cause disability or mortality. One of the factors associated with SSI was the abdominal wall thickness ≥20 mm. Therefore, the drainage of collection within subcutaneous tissue may decrease SSI rate. Objective: To compare SSI rate between patients with and without subcutaneous drain placement. Materials and Methods: The present study was prospective randomized controlled trial that included patients with abdominal wall thickness of 20 mm. or more and that underwent major abdominal operation between October 2015 and January 2018. The enrolled patients were randomized into two groups, with and without subcutaneous drain. Demographic data, operative details, characteristics of wound, and SSI rate were collected. The statistical tests were Chi-square test for categorical data and t-test for numerical data. Results: From 142 enrolled patients, 11 patients were excluded (four from death during follow-up and seven from incomplete data). Therefore, 138 were included and divided into 58 patients in the group with drain and 73 patients in the group without drain. The demographic data, operative time, subcutaneous thickness, and length of incision were not different. Regarding SSI, there was no significant difference between both groups (29.3% and 23.3%, p=0.44). Subgroup analysis within group of SSI patients, using drain showed significantly lower proportion of deep incisional SSI especially when subcutaneous thickness was 25 mm or more (18.8% and 53.8%, p=0.04) and estimated cut surface area of 4,500 mm² or more(8.3% and 50.0%, p=0.03). Conclusion: Subcutaneous drain placement did not decrease overall SSI rate. However, this modality provided lower proportion of deep incisional SSI when SST occurred especially in patients with thicker abdominal wall or larger cut surface area of surgical wound.