Purpose: The aim of this study was to evaluate the effect of off-axis implant placement in relation to the prosthetic crown on abutment screw loosening under different directions of twisting moments. Materials and Methods: Twenty-one implant assemblies were divided equally into three groups (n = 7). Each assembly consisted of an internal-octagon implant measuring 4.1 × 12 mm (standard plus implants) with corresponding 5.5-mm synocta abutments (Straumann) mounted in an epoxy resin-glass fiber composite. Group A had a straight implant configuration in relation to the prosthetic crown and was subjected to clockwise twisting moment (control). The other two groups, B and C, with off-axis implant placement were subjected to clockwise and counterclockwise moments, respectively. A lateral load of 80 N was applied to the specimens for 1 × 106 cycles at 90 degrees to the long axis of the implant. The loading point was 4 mm from the center of the implant in group A and 6 mm in groups B and C. The reverse torque value (RTV) of the abutment screw was measured before and after loading. Data were analyzed using a paired samples t test and one-way analysis of variance (ANOVA) at a significance level of α = .05. Results: An increase in postloading RTV was found relative to preloading RTV in all groups, but was only significant in group A (P .05). The mean reverse torque difference (RTD) was higher in group A (3.17 ± 1.04 Ncm), followed by groups B (1.03 ± 1.41 Ncm) and C (0.43 ± 1.09 Ncm). A significant difference in RTD was noted between group A and the remaining groups (P .05). However, no significant difference was found between groups B and C (P > .05). Conclusion: Placement of an implant in an off-axis relation to the prosthetic crown resulted in significantly lower reverse torque values compared with straight implant configuration. However, the extent of reduction in Ncm is small and is considered clinically insignificant in the studied implant system. Furthermore, no significant difference was found in RTV between clockwise and counterclockwise twisting moments. Keywords: implant cantilevers, lateral loading, off-axial loading, screw loosening