This study was aimed to compare the outcomes of two operational methods used for the fixation of calcaneal fracture, the open reduction using a plate and the minimally invasive cannulated screw fixations. Thus, we attempted to find out as to which of these fixation regimens was therapeutically superior by assessing improvement in the restoration of foot functioning and estimating the biochemical indices that reflect bone recovery. A total of 492 calcaneal fracture patients admitted in our hospital from February, 2008 to February, 2012 were selected for the study and randomly divided into two groups of 246 cases each. They were treated with either open reduction using a plate or minimally invasive cannulated screw fixation procedures. After the operations, patients were followed up for 2 years and the outcomes including functional restoration of calcaneus, the post-operational complications, and measure of the biochemical indicators of bone recovery were compared. The patients who underwent plate fixation procedure showed the excellent and good rate of 76.8 %. The minimally invasive cannulated screw fixation led to the excellent and good rate of 82.5 %. The angle, width, and height of calcaneus observed in the last follow-up were also improved significantly in the two groups (p < 0.05); however, these outcomes of the two techniques were not significantly different from each other (p > 0.05). The post-operative complications occurred with the rates of 14.2 and 4.9 % in the patients treated with the plate and the minimally invasive cannulated screw fixations, respectively. The length of stay and hospitalization costs in the plate fixation group were 9.16 ± 0.83 days and 12,639.74 ± 2,573.82 Chinese Yuan, respectively. In comparison, in cannulated screw fixation group, the length of hospital stay (7.03 ± 0.52 days) and its cost (6,795.01 ± 996.53 Chinese Yuan) were significantly lower. Serum bone alkaline phosphatase and tartrate-resistant acid phosphatase-5b levels measured at the last follow-up examination were significantly altered (p < 0.05) in the two groups. However, the difference between the outcomes of the two methods was not statistically significant (p > 0.05). Plate screw and the cannulated screw fixations showed equally good therapeutic effect and significantly improved patients' mobility. However, the cannulated screw fixation was superior in terms of post-operative infection-free recovery and economical burden to the patients.