Apart from the frequent conventional use of polyurethanes (PUs), synthesizing bio-based polyurethanes from renewable sources is a new exciting way. The most intriguing issue in this respect is the use of bio-based PUs in biomedical applications. In the present study, PU films were synthesized from castor oil (CO) and poly(ethylene glycol) (PEG) in different CO:PEG ratios with a different molecular weight of PEG. Procaine was chosen as a model drug. After the characterization of all films by FT-IR, DSC, and SEM methods, they were loaded with the drug in buffer solution at pH 9.1. The drug release behavior of the films in buffer solutions at pH 2.3, 5.8, and 6.4 was determined. Their swelling and degradation behaviors were also determined to explain their drug release mechanism. We found that decreasing the molecular weight of the PEG improved the drug release. Additionally, CO:PEG ratio and medium pH are critical factors for the release behavior of the films. Almost 100% of the total drug was released at pH 2.3 in 24 h, which was approximately more than three-fold than that at pH 6.4. Zeroorder, first-order, Higuchi, Korsmeyer-Peppas, and Kopcha kinetic models were used for the evaluation of the release data.