Background and Objectives: A difficult gallbladder anatomy augments the risk of bile duct injuries (BDIs) and other complications during a laparoscopic cholecystectomy. This study compares the outcomes of a laparoscopic subtotal cholecystectomy (LSTC) and open total cholecystectomy (OTC) for difficult cholecystectomies. Materials and Methods: This retrospective analysis of gallbladder procedures (LSTC or OTC) from 2016 to 2023 examined patient demographics, surgical details, and postoperative results. The primary outcome was the incidence of a BDI. Secondary outcomes included operative duration, blood loss, and postoperative complications. Results: Seventy-one patients were included in the study. Of them, 59.2% (n = 42) underwent an LSTC and 44.6% (n = 29) underwent an OTC. The LSTC cohort was more likely to have a day-surgery case with a same-day discharge (33.3% vs. 0%, p = 0.009), less blood loss (71.4 ± 82.26 vs. 184.8 ± 234.86, p = 0.009), and a shorter operative duration (187.86 ± 68.74 vs. 258.62 ± 134.52 min, p = 0.008). Furthermore, BDI was significantly lower in the LSTC group (2.4% vs. 17.2%, p = 0.045). However, there were no significant differences between the two groups concerning intraoperative drain placement, peri-cholecystic fluid collection, bile leak, and other complications (p > 0.05). Conclusions: LSTC is a safe and effective alternative to OTC for challenging gallbladder cases. Further studies with larger sample sizes and longer follow-up periods as well as different study designs are warranted.