Objective To compare the effectiveness of two minimally invasive methods: minimally invasive plating osteosynthesis (MIPO) and expandable intramedullary nail ing technique in treatment of middle third humeral shaft fractures. Methods The cl inical data were retrospectively analyzed and compared from 33 cases with middle third humeral shaft fractures between May 2004 and December 2008. All the patients were divided into 2 groups: 14 patients were treated with MIPOtechnique (group A) and 19 with expandable intramedullary nail ing technique (group B). In group A, there were 10 males and 4 females with an average age of 35 years (range, 21-51 years). The disease cause was traffic accident in 5 cases, tumbl ing in 6 cases, machine related trauma in 2 cases, crushed by a heavy object in 1 case. Six fractures were classified as AO type A, 6 as type B, and 2 as type C. The time from injury to operation was 3 to 11 days with an average of 5.9 days. In group B, there were 12 males and 7 females with an average age of 40 years (range, 19-68 years). The disease cause was traffic accident in 7 cases, tumbl ing in 8 cases, fall ing from height in 3 cases, crush injury in 1 case. Ten fractures were classified as AO type A, 8 as type B, and 1 as type C. The time from injury to operation was 2 to 6 days with an average of 4.2 days. There was no significant difference in general data between 2 groups (P gt; 0.05). Results The operation time was (104.6 ± 25.8) minutes in group A and (85.0 ± 35.7) minutes in group B, showing no significant difference (P gt; 0.05). Incision healed by first intention without iatrogenic radial nerve palsy in 2 groups. The patientswere followed up 21.4 months on average (range, 12-37 months) in group A and 20.5 months on average (range, 22-35 months) in group B. The X-ray films showed bony heal ing in all patients. The fracture union time was (16.4 ± 6.1) weeks in group A and (15.0 ± 2.5) weeks in group B, showing no significant difference (P gt; 0.05). The University of Cal ifornia Los Angeles (UCLA) End- Result scores were 34.1 ± 1.1 in group A and 31.8 ± 2.6 in group B and the Mayo Elbow Performance scores were 100 in group A and 97.6 ± 3.9 in group B; all showing significant differences (P lt; 0.05). Conclusion Good cl inical outcomes could be obtained when middle third humeral shaft fractures are treated by either MIPO or expandable intramedullary nail ing techniques. However, MIPO technique could offer better shoulder and elbow functional results.