Acute pain is a common symptom experienced by all children. Pain may be due to different causes, but inflammatory pain is the most common. In addition, infectious diseases are characterized by an inflammatory reaction. As a result, inflammatory pain, including pain associated with infections, should be preferably relieved by non-steroidal anti-inflammatory drugs (NSAIDs). In this regard, ketoprofen and ketoprofen lysine salt represent a valuable option also in children with mild-moderate acute pain. This paper presents and discusses the comparative studies between ketoprofen or KLS and other analgesics, mainly concerning ibuprofen and acetaminophen. The results showed that ketoprofen and KLS are an effective, safe, and rapid strategy in relieving mild-moderate acute pain in children.