Purpose: The aim of this in vitro study was to evaluate, by means of strain gauge analysis, the effect of different implant diameters on strain around two-implants retaining a mandibular over denture with locator attachments .   Methods:three acrylic models with silicon mucosal simulation was fabricated and two laboratory implnts were inserted in canine areas. According to implant diameter, the experimental casts were randomly divided into 3 groups, (GI) large(4.2mm), (GII) medium(3.7mm),(GIII) small (3.3mm) and all implants had a length of 13mm. three dentures were fabricated and connected to implants with locator attachments. Four linear strain gauges were bonded to the acrylic resin at mesia, distal, buccal, lingual surfaces of each implant. 100 N static load was applied uni laterally over first premolar and molar positions. Strains were measured at mesial, distal, buccal, lingulperi-implant sites t loading (right) and non loading (left) . Results: The results showed that for loading and non-loading side, for majority of surfaces and for both premolar and molar positions small diameter implants recorded the highest strain, followed by medium diameter implants and the smallest strain was recorded with large diameter implants. Conclusions:The highest strain was recorded with small diameter implants, followed by medium diameter implants and the lowest strain was recorded with large diameter implants. Therefore, it is recommended to use the largest implant diameter as possible to minimize peri-implant strain when locator attachments are used to retained mandibular overdentures to implants.The highest strain recorded at lingual surface on first premolar loading and at distal surface during first molar loading.Frist premolar loading was associated with significant higher strain than first molar loading.Randomized controlled clinical trials are needed to evaluate the effect of different implant diameters on peri-implant crestal alveolar bone loss.