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Hydrogels that can undergo gelation upon injection in vivo are promising systems for the site-specific delivery of drugs. In particular, some thermo-responsive gels require no chemical additives but simply gel in response to a change from a lower temperature to physiological temperature (37 °C). The gelation mechanism does not involve covalent bonds, and it is possible that incorporation of drugs into the hydrogel could disrupt gelation. We investigated the incorporation of drugs into thermo-responsive hydrogels based on poly(ϵ-caprolactone-co-lactide)-block-poly(ethylene glycol)-block-poly(ϵ-caprolactone-co-lactide) (PCLA–PEG–PCLA). Significant differences in properties and in the response to incorporation of the anti-inflammatory drug celecoxib (CXB) were observed as the PEG block length was varied from 1500 to 3000 g mol−1. Linear viscoelastic moduli of a PCLA–PEG–PCLA hydrogel containing a 2000 g mol−1 PEG block were least affected by the incorporation of CXB and this gel also exhibited the slowest release of CXB, so the incorporation of phenylbutazone, methotrexate, ibuprofen, diclofenac and etodolac was also investigated for this hydrogel. Different drugs resulted in varying degrees of syneresis of the hydrogels, suggesting that they interact with the polymer networks in different ways. In addition, the drugs had varying effects on the viscoelastic and compressive moduli of the gels. The results showed that the effects of drug loading on the properties of thermo-responsive hydrogels can be substantial and depend on the drug. For applications such as intra-articular drug delivery, in which the mechanical properties of the hydrogel are important, these effects should thus be studied on a case-by-case basis.