Patients with palliated tetralogy of Fallot (TOF) often require pulmonary valve replacement in adulthood, yet the data regarding their outcomes are scarce. This study aimed to identify risk factors associated with postoperative complications in these patients and to establish long-term survival data for this patient group. A retrospective cohort study investigated 153 consecutive patients with a history of TOF repair who underwent pulmonary valve replacement at a single large academic center between March 1996 and March 2010. In part 1 of the study, logistic models were constructed to assess demographic, medical, and surgical risk factors for operative mortality; occurrence of a major adverse event (stroke, renal failure, prolonged ventilation, deep sternal infection, reoperation, or operative mortality); and prolonged hospital stay (>7 days). Risk factors with a p value less than 0.10 by univariate analysis were included in the subsequent multivariate analysis. In part 2 of the study, long-term, all-cause mortality was determined by construction of a Kaplan–Meier curve for the cohort. Seven patients died (4.5%). Significant risk factors for mortality in the multivariable analysis included age older than 40 years (odds ratio (OR) 9.89) and concomitant surgery (OR 6.65). A major adverse event occurred for 22 patients (14.4%). The only significant risk factor in the multivariable analysis for an adverse event was concomitant surgery (OR 6.42). The hospital stay was longer than 7 days for 31 patients (20.3%). The significant risk factors for a prolonged hospital stay included the presence of preoperative arrhythmias (OR 4.17), New York Heart Association class 3 (OR 4.35), and again, concomitant surgery (OR 4.2). Among the 146 hospital survivors, only 5 patients died in the intervening period. The predicted survival rates were 98.5% at 1 year, 96.7% at 5 years, and 93.5% at 10 years. Pulmonary valve replacement in adults with palliated TOF is a safe procedure with excellent long-term survival, but there remain important risk factors for postoperative mortality, prolonged hospital stay, and major adverse events. Awareness and modification of important risk factors may help to improve outcomes.