Background: The introduction of biosimilar colony-stimulating factors has led to the reduction in prices for these historically expensive therapies. To understand the impact of recent pricing trends on delivering efficient care, the cost-effectiveness of primary prophylaxis (PP) versus secondary prophylaxis (SP) using pegfilgrastim was assessed in patients with breast cancer, non–small-cell lung cancer (NSCLC), and non-Hodgkin lymphoma (NHL) receiving potentially curative chemotherapy at intermediate risk for febrile neutropenia per NCCN guidelines. Methods: A Markov decision analytic model was constructed from the US payer perspective over a lifetime horizon to evaluate pegfilgrastim PP versus SP in patients with breast cancer, NSCLC, and NHL receiving curative chemotherapy at intermediate risk of FN. Modeled chemotherapy regimens were adjuvant docetaxel (breast cancer), adjuvant carboplatin/paclitaxel (NSCLC), and R-CHOP (NHL) representing baseline FN risk of 16%, 18%, and 18%, respectively. Historical average sales prices (ASP) according to the Centers for Medicare and Medicaid Services of all pegfilgrastim products were obtained from January 2017 to April 2021. When more than one pegfilgrastim product was available, the average ASP was used as the cost input for the model. Cost-effectiveness for the base case scenario of each cancer type was evaluated over the range of years for cost per quality-adjusted life year (QALY) gained. Results: Pegfilgrastim as PP vs. SP provided an additional 0.069, 0.112, and 0.166 QALYs for breast cancer, NSCLC, and NHL, respectively. The peak ASP for pegfilgrastim was $4,554 per 6 mg during July 2018. Afterwards, a linear regression observed a declining ASP of approximately $134 dollars every 3 months to $3,024 per 6 mg during April 2021. At peak ASP, the incremental cost-effectiveness ratios (ICERs) for pegfilgrastim PP in patients with breast cancer, NSCLC, and NHL were $200,320, $113,942, and $103,495 per QALY, respectively. For April 2021, the ICERs were $124,845, $67,294, and $57,269 per QALY, respectively (Table). Conclusions: The trend of decreasing pegfilgrastim ASP improved the cost-effectiveness of PP vs. SP across intermediate risk breast cancer, NHL, and NSCLC indications between July 2018 to April 2021. For the most recent ASP, PP was cost-effective at a willingness-to-pay threshold of $100,000/QALY for NSCLC and NHL, and $150,000/QALY for breast cancer. This analysis provides support to expand the use of growth factor PP to intermediate risk patients.