Over the last decades, minimally invasive surgery (MIS) techniques entered in the surgical routine due to their major advantage in reducing the unnecessary exposure of tissue and, thus, the trauma. Even in the context of orthopedics and spine surgery these practices have been widely developed and applied. Besides the clinical outcome of the patients, few studies have quantitatively assessed the traumatic and inflammatory effects of a specific surgical technique. Indeed, currently, a universally accepted biological outcome measure, such as a panel of biochemical markers, to define the success of MIS approach is still lacking. We reviewed the literature to collect the published data regarding the quantitative analysis of trauma induced by either conventional or minimally invasive surgery with the aim of highlighting evidence useful to guide future studies. Previous publications show some evidence in support of the hypothesis that MIS approaches are less traumatic, and possibly less pro-inflammatory, than conventional ones. Creatin kinase (as a marker of muscular damage) and C-reactive protein (as a marker of systemic inflammation) seem to reproducibly follow different trends in minimally invasive surgery compared to conventional procedures. Moreover, cytokines, such as interleukin (IL)-6 and IL-10 are also promising markers in this context.