Background: s/Aims: The effect of preoperative biliary drainage (PBD) on outcomes for pancreaticoduodenectomy (PD) patients with moderate jaundice (10–15 mg/dL) remains understudied. While PBD aims to improve hepatic function, it may increase morbidity due to infections. Methods: This study analyzed PDs performed between July 2022 and 2025. Patients with periampullary cancers and bilirubin levels of 10–15 mg/dL were included. We compared patients who underwent upfront PD (upfront surgery [UP] group) with those who received PBD (via endoscopic retrograde cholangiopancreatography or percutaneous transhepatic biliary drainage) regarding perioperative outcomes, morbidity, mortality, bile microbiology, antibiotic use, and costs. Results: Among 92 PD patients, 40 met the inclusion criteria (UP = 16; PBD = 24). Baseline characteristics were comparable, except for higher bilirubin levels in the UP group (12.6 mg/dL vs. 1.35 mg/dL, p = 0.001). The PBD group exhibited a harder pancreatic texture (58.3% vs. 25.0%, p = 0.03), higher surgical site infections (SSIs) (70.8% vs. 18.7%, p = 0.001), and a greater incidence of positive bile cultures (75% vs. 25.0%, p = 0.001). Overall morbidity, Clavien-Dindo grade 3 complications, and 90-day mortality rates were similar between the groups. However, antibiotic costs were significantly higher in the PBD group (₹31,047 vs. ₹20,937; +50%). Conclusions In patients with moderate jaundice (10–15 mg/dL), upfront PD can be performed safely. Routine PBD offers no clinical benefit and is associated with higher rates of SSIs, bile contamination, and increased costs.