Background Previous clinical studies have generally reported that prophylactic cranial irradiation (PCI) was given to patients with a complete response (CR) to chemotherapy and chest radiotherapy in limited-stage small-cell lung cancer (SCLC). It is not clear if those with incomplete response (IR) would benefit from PCI. Patients and Methods The Saskatchewan experience from 1981 through 2007 was reviewed. Patients were treated with chest radiotherapy and chemotherapy with or without PCI (typical doses: 2500 cGy in 10 fractions over 2 weeks, 3000 cGy in 15 fractions over 3 weeks, or 3000 cGy in 10 fractions over 2 weeks). Results There were 289 patients treated for curative intent, 177/289 (61.2%) of whom received PCI. For the whole group of 289 patients, PCI resulted in significant overall survival (OS) and cause-specific survival (CSS) benefit (P = .0011 and 0.0005, respectively). The time to symptoms of first recurrence at any site with or without PCI was significantly different: 16.9 vs. 13.2 months (P = .0006). PCI significantly delayed the time to symptoms of first recurrence in the brain: 20.7 vs. 10.6 months (P < .0001). The first site of metastasis was the brain for 12.5% and 45.5% patients with CR with and without PCI, respectively (P = .02) and in 6.1% and 27.6% of patients with IR with and without PCI, respectively (P = .05). For the 93 patients with IR, PCI did not confer OS or CSS benefit (P = .32 and 0.39, respectively). Conclusions Patients with IR benefited from PCI, with a reduced rate of and a delayed time for the development of brain metastases, although without significant OS or CSS benefit. PCI could be considered for all patients with limited-stage SCLC responding to chemoradiation.