The prevalence of chronic otitis media with effusion (COME) in children with down syndrome (DS) has been reported to be 93% by age 1 and 68% by age 5 [1,2]. Eustachian tube (ET) dysfunction, impairing the ability of the middle ear to clear fluid and equalize middle ear pressure, is thought to be more severe and prolonged in children with DS. This is likely due to multiple factors including craniofacial abnormalities, reduced density of ET cartilage predisposing to collapse, and generalized hypotonia affecting palatal muscles that open the ET [2,3]. ET dysfunction predisposes DS children to fluctuating and persistent conductive hearing loss due to middle ear effusion. It is estimated that chronic otitis media with effusion (COME) with conductive loss occurs in 80% of children with DS [4]. Placement of tympanostomy tubes (TT), is standard treatment for COME and has been demonstrated to improve hearing levels in 93% of children with DS by one year after TT placement [5]. Given the propensity and persistence of COME in DS, some affected children will require repeated TT insertions. DS children requiring 3 or more sets of TT are reported to have increased rates of chronic perforation, retraction pockets, atelectasis, and cholesteatoma [4]. Although the exact incidence of cholesteatoma in children with DS is unknown, it has been suggested that acquired cholesteatoma may occur more commonly and may be more extensive at time of diagnosis than in children without multiple risk factors for ET dysfunction [6,7]. Ear examinations in those with DS can be more challenging for clinicians due to narrow external auditory canals and poor patient cooperation, potentially delaying diagnosis. Surgery to excise cholesteatomas may also be difficult due to narrow ear canals and poorly developed, sclerotic mastoid anatomy. The goal of this retrospective review is to analyze our experience with cholesteatoma management in children with DS seen at a tertiary care children’s hospital over the last decade. The analysis will focus on diagnostic challenges and findings, surgical challenges and outcomes, recurrence rates, postoperative hearing outcomes, and complications associated with the cholesteatoma or surgical interventions.