Purpose To compare the efficacy and safety of hydroxyapatite vs. bone pate as obliteration material in mastoidectomy surgery for patients with chronic suppurative otitis media and cholesteatoma. Methods This is a retrospective, multi-center, cohort study. All patients were followed up with micro-otoscopy, audiometry, and, if indicated, MRI with diffusion-weighted imaging. The following outcome parameters were analyzed: procedure safety (wound infections and complications), cholesteatoma recidivism rates (residual/recurrent), control of infection (Merchant's scale), and hearing results (pure-tone averages at 500/1000/2000/4000 Hz). Results Eighty-three cases were included: 45 obliterated with hydroxyapatite and 38 with bone pate, with a mean follow-up time of, respectively, 25 and 24 months. Wound infections were only detected in the bone pate group (4.8%) and successfully treated with oral or intravenous antibiotics and surgical drainage (p = 0.026). No other major surgical complications were observed in both groups. Cholesteatoma recidivism was observed in 15% using hydroxyapatite and 12% using bone pate (p = 0.471). Complete control of infection (Merchant 0) was achieved in 76.2% using bone pate and 86.8% using hydroxyapatite at 12 months postoperatively (p = 0.223). All patients showed good postoperative healing without complete failure to manage infection (Merchant 3). Pre- and postoperative audiometry showed significant improvement in hearing results in both groups. No significant difference between the obliteration materials was observed. Conclusions Evaluation of mastoid obliteration reveals that hydroxyapatite and bone pate are safe and effective obliteration materials, with high success rates in achieving a dry ear, low recidivism rates, and good hearing outcome, respecting the short-term limitation. In addition, our study shows that hydroxyapatite results in fewer postoperative wound infections compared to bone pate.