Introduction: Axis of loading can impact the effect of abutment fit to implant, thereby affecting the implant-abutment screw joint preload leading to screw loosening. Aim: The aim of the in-vitro study was to comparatively evaluate the effect of cyclic loading on abutment screw loosening of 25 degrees angled premachined titanium abutments with that of 25 degrees angled custom cast cobalt chromium (Co-Cr) abutments. Materials and Methods: Premachined titanium abutments (Group I) and custom cast cobalt-chromium abutments (Co-Cr) (Group II), 10 each of 25 degrees angulation were connected to their respective titanium implants mounted in stainless steel blocks. Cement-cum-screw retained nickel-chromium cast crowns were fabricated. Abutment screws were torqued to 35 Ncm. Reverse torque values were measured using digital torque meter before and after cyclic loading simulating six months of function. The results were statistically analysed using Paired t-test and Independent t-test. Results: Mean pre-cyclic loading reverse torque values were 28.96 Ncm (Group I) and 26.01 Ncm (Group II) and mean post-cyclic loading reverse torque values were 25.84 Ncm (Group I) and 23.82 Ncm (Group II) respectively. Cyclic loading resulted in significantly lesser reverse torque values within both test groups (p<0.01). There was significantly greater loss of preload for Group II samples both prior to and after cyclic loading compared to Group I samples (p<0.01). Conclusion: Cyclic loading resulted in significant screw loosening within both test groups. Screw loosening was found to be significantly less for angled premachined titanium abutments than for angled custom cast Co-Cr abutments both before and after cyclic loading. The study is clinically significant regarding the importance of screw joint-abutment connection acting in a maxillary anterior implant region under load and the consequences of poor connection. The study is important in the aspect of clinical implications of angled implant abutments and the effect of loading on them.