To analyze the involvement of disease in pterygopalatine fossa (PPF), its relation to regional extension of disease and the treatment outcome in rhino-oculo-cerebral mucormycosis (ROCM). A prospective study was done including 50 patients diagnosed with ROCM. All patients were examined and evaluated with high resolution CT and MRI imaging. Intravenous liposomal Amphotericin B was started, and endoscopic debridement was done based on the disease extension. Liposomal Amphotericin B is given until complete response for atleast a total dose of 3-4 g. T. Posaconasole 300 mg is given for 3-4 months in case of orbital or intracranial disease. 58% (29) patients showed involvement of disease in PPF. In MRI T1 contrast images, 21 of these patients showed hypo-intense lesion in the PPF and had necrotic tissue in PPF during surgery. Whereas, hyper-intense lesion that depicts inflammatory tissue was seen in the 8 patients. The tissue from these lesions showed aseptate fungal hyphae elements in histopathology in all these patients. 96% of patients with orbital mucormycosis (25 patients), 92% of patients with palatal mucormycosis (24 patients) and all patients with intracranial (15 patients) involvement had correlating PPF involvement in the disease process. The pterygopalatine fossa is the nidus for spread of disease and an important prognostic factor for extent of spread. Radiological imaging with CT and MRI are useful to assess the involvement of disease in PPF, and it is important to remove this disease during endoscopic debridement.