Quantitative lytA realtime (rt) PCR from nasopharyngeal (NP) swabs distinguishes pneumococcal pneumonia (CAP) from asymptomatic colonization. Use of an optimized cut-off increased pneumococcal etiology compared to traditional diagnostic methods. Here we compare the utility of lytA rtPCR from induced sputum and from NP swabs. Methods: Pneumococcus was considered the cause of CAP in HIV-infected South African adults, if any of blood culture, induced sputum culture or Gram stain, urine antigen, whole blood lytA rtPCR revealed pneumococcus or if NP lytA rtPCR was >8000 copies/ml. lytA rtPCR was also performed on induced sputum. Results: 149 (67.1%) of 222 patients with available induced sputum had pneumococcus detected by lytA rtPCR from sputum, whereas either sputum Gram stain or culture were positive in 105 of 229 patients (45.9%; p<0.001). Mean copy numbers from sputum were higher if sputum cultures were positive than if sputum cultures were negative (7.9 vs. 5.6 log10 copies/ml; p<0.001). Against the composite diagnostic standard, a 10000 copies/ml cut-off for good quality sputum lytA rtPCR had a sensitivity of 78.1% and a specificity of 80.0%. This cut-off performed similarly well as the previously identified 8000 copies/ml cut-off for NP swab lytA rtPCR (AUC-ROC: 80.4% for any quality sputum vs. 79.6% for NP swab). The AUC-ROC for good quality sputum was 83.2%. Conclusions: Overall lytA rtPCR performs similarly well on induced sputum as on NP in most patients, but slightly better if good quality sputum can be obtained. Due to the ease of specimen collection, NP swabs may be preferable for the diagnosis of pneumococcal pneumonia.