Patients (pts) with oligometastases (≤5 lesion sites) treated with SBRT have demonstrated evidence of long-term disease-free survival despite the overall poor prognosis of metastatic disease. Nelfinavir is a HIV protease inhibitor that may potentially act as a radiosensitizer. We performed a Phase II study of nelfinavir concurrent with SBRT in pts with solid tumor oligometastases to determine 6-month (6mo) freedom from local progression (FFLP). Secondary endpoints include safety, overall survival (OS), freedom from distant metastasis (FFDM) and progression-free survival (PFS). Pts with ≤5 histologic confirmed metastatic lesions (≤ 5.0 cm or ≤250 cm3) of lung, liver, lymph nodes, or bone, and good performance status (ECOG ≤ 2) were eligible. Pts were given 1250 mg of nelfinavir twice daily for 7 days prior to and after a single dose of 15 Gy SBRT per lesion. Responses were evaluated based on RECIST 1.1 criteria. A total of 38 pts were accrued between January 2014 and December 2015. One withdrew consent and 37 were included in the analysis, with a median follow-up of 18 months (range 5-31.5 months). The median patient age was 65 (range 35-81 years), 62% were men, and 51% and 22% had prostate and sarcoma as primary histologies, respectively. The majority of pts had ≤3 lesion sites (54% had 1 lesion, 22% had 2, and 16% had 3), and had recurrence sites at bone (57%) or lung (24%). The 6 mo FFLP rate was 78.4% (95% CI: 61.4-88.5%). Among the 68 treated lesions, the 6mo FFLP rate by lesion was 76.5% (95% CI: 64.5-84.9%). There were a total of 3 deaths due to disease progression. The 18 mo rates of OS, FFDM, and PFS were 90.7% (95% CI: 73.8-96.9), 62.4% (95% CI: 43.9-76.3), 57.6% (95% CI: 39.7-72.0), respectively. The 6 mo FFLP rate for patients with prostate cancer was 100% compared to 63% for patients with sarcoma (P < 0.0003). There were 4 grade 3 adverse events that may have been related to treatment (e.g., absolute lymphocyte decrease, anxiety, nausea, and cough). SBRT can be delivered safely with nelfinavir. Overall 6 mo FFLP rate for the entire cohort was not significantly higher than historical controls, although this may be secondary to tumor histology, treated site, and lesion number. Prostate cancer patients had significantly improved clinical outcomes relative to sarcoma patients and thus one may hypothesize that certain histologies may require a higher SBRT dose for local control. Further research should be conducted into the optimum patient cohort to benefit from the concurrent use of radiosensitizers with SBRT.