Many of the non-steroidal anti-inflammatory drugs (NSAIDs) currently marketed produce severe gastro-toxic side effects. The benefits of producing NSAIDs without these side effects are obvious, particularly for patients requiring long-term therapy. The aim of this investigation was to produce novel NSAIDs, based on paracetamol, that exhibit little or no gastro-toxicity. The work covers design, synthesis and testing of 13 drug candidates. The analgesic and anti-inflammatory potencies of the drug candidates were measured using the mouse abdominal constriction assay and the carrageenan-induced rat paw oedema assay, respectively. The stomachs of the rats were examined post-mortem, to assess the gastro-toxicity of the drugs. Of the 13 compounds described herein, 11 were shown to possess analgesic activity at 2-10 times the potency of aspirin, while 8 demonstrated anti-inflammatory activity at 3-10 times the potency of aspirin. Significantly, all of the compounds showed very low gastro-toxicity when compared with aspirin. The results of this study indicate that it is possible to develop novel, potent NSAIDs based on the structure of paracetamol. These compounds have the advantage of demonstrating much lower gastro-toxicity than NSAIDs currently available. Drugs of this type may, in future, provide effective treatments for inflammatory disorders.