Xpert MTB/RIF-generated cycle-threshold (C(T)) values have poor clinical utility as a rule-in test for smear positivity (cut-point ≤20.2; sensitivity 32.3%, specificity 97.1%) but moderately good rule-out value (cut-point >31.8; negative predictive value 80.0%). Thus, 20% of individuals with C(T) values >31.8 were erroneously ruled out as smear-negative. This group had a significantly lower sputum bacillary load relative to correctly classified smear-positive patients (C(T) ≤ 31.8; P < .001). These data inform on public health and contact tracing strategies.