Oral non-steroidal anti-inflammatory drugs (NSAIDs) are used for relief of joint pain during and post-exercise. However, they increase the risk of systemic adverse events (AEs), even in healthy individuals, and retard recovery from muscle soreness. TDT 064, a topical formulation containing ultra-deformable drug-free Sequessome™ vesicles, has shown equivalent efficacy to oral celecoxib in reducing osteoarthritis (OA)-associated joint pain and stiffness and does not cause NSAID-related AEs. TDT 064 (Flexiseq® Sport), has recently been shown to improve recovery from muscle pain post-exercise versus an oral NSAID. Participants (n = 168) with a pain score ≥3 (10-point scale) 12–16 h post-exercise were randomised to receive TDT 064 + oral placebo, TDT 064 + oral ketoprofen, or ketoprofen in ultra-deformable phospholipid vesicles + oral placebo. Pain scores were significantly lower with TDT 064 + placebo than with oral ketoprofen + TDT 064 in the 7 days post-exercise (p = 0.0240) and muscle soreness recovery was significantly shorter (p = 0.0262). There was a low incidence of AEs. These data are supported by clinical experience. A 24-year-old professional rugby player suffered a lisfranc fracture in March 2014 and underwent operative reconstruction. He had no relevant medical history or concomitant medications. He reported restricted training due to pain (score 7/10), stiffness (score 9/10) and poor function, and pain when changing direction and running on consecutive days. In July 2014 he began using TDT 064 bid (recommended dose). In November 2014 he noted reduced pain on running (score 2–3/10), decreased stiffness (score 4/10) and improved mobility, without AEs, and he was able to return to competitive rugby. TDT 064 shows efficacy against exercise- and injury-induced joint pain, as well as OA-associated pain. It does not retard muscle soreness recovery after exercise compared with an oral NSAID, making it an alternative treatment for joint pain during and post-exercise.