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Background Rheumatic heart disease (RHD) is endemic in Tanzania and is ranked third among the most common causes of heart failure after hypertensive heart disease and cardiomyopathy. This study aimed to determine the predictors of early operative mortality for RHD at Muhimbili National Hospital, Tanzania. Methods In this retrospective cross-sectional study, 212 patients operated on due to RHD from May 2008 to December 2012 were included. The patients’ demographic and clinical data at admission and within 30 days of their respective index elective cardiac procedures were recorded in a predefined clinical record form. The chi-square test and Fisher’s exact test were used to compare categorical variables. Variables with a P value <0.2 in the bivariable analysis were included in a multivariable modified Poisson regression model. Results Of the 212 patients, 140 (66%) were females. The median age was 21 years (interquartile range, 15-32 years). One hundred forty-five patients (68.4%) underwent valve replacement, of which 113 (77.9%) were single (mitral), 17 (11.7%) aortic, and 15 (10.4%) double (aortic and mitral) valve replacements. Valve repair was performed on 42 patients (19.8%), 41 of whom had mitral repairs and 1 of whom had an aortic repair. Surgical mitral commissurotomy was performed on 25 patients (11.8%). Thirty patients (14.1%) died in hospital. In multivariable analysis, mortality was >5 times higher among patients who underwent double than single valve replacement (adjusted prevalence ratio, 5.65; 95% confidence interval, 2.46-12.99; P<0.001). Patient age, disease duration, ejection fraction, surgical modality, pulmonary hypertension, and intensive care unit stay were not predictors of mortality. Conclusions The in-hospital mortality observed in this study was higher than those reported in previous studies. In patients with RHD, double valve replacement is associated with increased early mortality, which may require greater technical expertise and careful postoperative management. Our findings need to be confirmed in prospective studies. [ABSTRACT FROM AUTHOR]