Physiotherapists are primary care practitioners, and are often the first health professional to consult with patients presenting with acute sprains or strains, and such patients may ask for advice regarding medications. Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) are readily available without a prescription and are commonly used by patients. The aim of this study was to investigate New Zealand physiotherapists' knowledge regarding the comparative safety, effectiveness, and appropriate timing of paracetamol and NSAIDs for acute musculoskeletal sprains and strains. A questionnaire was mailed to all members of the New Zealand Society of Physiotherapists currently practicing in the field of musculoskeletal physiotherapy (n = 948). Of 278 respondents (29.3%), just over half (52%) thought that NSAIDs were more effective than paracetamol in the treatment of sprains and strains. Almost half (45%) believed that NSAIDs should be withheld because of the potential for interrupting the beneficial role of inflammation in healing and that NSAIDs could increase bleeding into the injured tissue. In contrast, the majority of respondents (81%) recognised that there was no need to withhold paracetamol in the initial postinjury period. Knowledge regarding safety, effectiveness, and risks of paracetamol and NSAIDs may assist physiotherapists to recommend appropriate management of acute musculoskeletal injuries, within regulatory boundaries.