Background: Studies of patients age < 65 suggest large increases in utilization and costs of targeted anti-cancer drugs (TADs). However, use and costs of TADs in patients age 65+ have not been examined in a national sample. Methods: We conducted a retrospective analysis of patients ≥ 65 years with invasive lung (LC), breast (BC), or colorectal (CC) cancer using Medicare 5% claims from 2004-2015. We identified the yearly proportion of cancer patients receiving an intravenous TAD and the proportion of Part D enrolled Medicare patients receiving an oral TAD. We examined yearly costs of TADs as a proportion of total Medicare cancer and all-cause spending. Using generalized linear models, we estimated yearly trends in mean cost per beneficiary for TADs, all cancer spending, and total Medicare cost with adjustment for age, sex, region and comorbidities. Costs were adjusted to 2015 dollars using the CPI medical cost index. Results: We observed higher uptake of IV TADs in the 65+ patient population for each of the three cancers compared to oral TADs. IV TAD utilization reached 9.8% in CC patients, 5.0% in lung cancer patients, and 3.7% of BC patients. Use of oral TADs remained lower than use of IV TADs (≤ 1% of patients across all three cancers). From 2005-2015, total and cancer-specific Medicare spending per beneficiary decreased slightly for CC and LC patients and remained stable for BC patients. However, adjusted mean IV TAD spending per beneficiary increased from $139 in 2005 to $897 in 2015 for LC, from $96 to $550 for BC, and from $384 to $455 for CC. For Part D patients, the combined contribution of IV and oral TADs to total yearly cancer spending increased significantly from 2006 to 2015 for LC (2 to 5%), BC (4 to 18%), and CC (6 to 12%) cancers. Conclusions: Use of IV TADs in the US elderly lung, breast, and colorectal cancer populations grew rapidly in the years following FDA approval and stabilized. Use of oral TADs remained low compared to IV agents. Against the backdrop of largely stable Medicare spending, TADs are increasingly responsible for a growing proportion of that spending, particularly in breast cancer patients where TADs accounted for nearly a fifth of all 2015 cancer spending for Part D patients.