As an injection-based medical procedure, prolotherapy carries risk of injection-related side effects or adverse events, similar to those of other injection techniques. This risk is minimized through appropriate training and conduct.

The main risk of injection-based therapy is pain, and mild bleeding or bruising as an outcome of needle-related trauma. Patients may report pain, tissue ‘fullness’ and occasional numbness at the injection site at the time of therapy. These symptoms are typically self-limited and short-lived; prolotherapy is generally well-tolerated. Post-injection pain that persists after prolotherapy session for up to 72 hours is less common, with clinical trials reporting that approximately 10% of participants experience such pain. This is typically self-limited as well and responds to non-prescription medications such as acetaminophen.

All injection procedures, including prolotherapy, carry the risk of infection. Fortunately, this risk is minimized by following appropriate infection control procedures. In its university-based education and service learning programs, the University of Wisconsin Prolotherapy Education and Research Lab (UW-PEARL) and the Hackett Hemwall Patterson Foundation teach and use a comprehensive set of standard techniques to prevent infection, including the spread of bloodborne pathogens. This includes the use of universal precautions to avoid direct contact with bodily fluids, aseptic technique during procedures, and numerous procedures designed to safely store, handle, transfer and dispose of injected solutions, needles and procedural equipment.

Prolotherapy, like other injection therapies, also carries risk specific to the anatomical location of the injection; condition-specific risks should be discussed with the practicing physician. Prolotherapy is a treatment modality that can reduce pain and improve function in well-selected patients and is safe when performed by appropriately trained clinicians.