Abstract Background Karydakis flap (K-flap) and excision with healing by secondary intention (EHSI) are currently accepted methods for surgical management of sacrococcygeal pilonidal disease. This clinical trial study aimed to compare early and late outcomes of these two surgical techniques. Materials and methods In this controlled, prospective, randomized clinical trial, patients diagnosed with sacrococcygeal pilonidal disease were randomly allocated to two groups. Patients in the first group underwent Karydakis procedure, whereas EHSI was the surgical management in the second group. The two techniques were compared based on their overall time of wound healing, return to work, rate of complications, and recurrence. Results A total of 321 patients including 161 in the K-flap group and 160 in the EHSI group were included in the study. The median follow-up duration was 49 mo. The mean time of wound healing (16.44 versus 80.01 d, P  < 0.001), return to work (14.44 versus 24.19, P  < 0.001), rate of wound complications (18.7% versus 31.2%, P  = 0.006), and recurrence (1.2% versus 7.5%, P  = 0.005) were all significantly lower in the K-flap group. The mean operation time was significantly shorter in the EHSI group (15.87 versus 55.17 min, P  < 0.001). The K-flap group showed significantly higher pain on their first postoperative day and significantly less pain after 1 wk ( P  < 0.001). Conclusions Although both techniques are safe, the K-flap is associated with significantly lower rates of complications and recurrence and significantly shorter time of wound healing and return to work.