Background: Total knee arthroplasty (TKA) has been known as a definitive treatment of advanced knee osteoarthritis. Both intra- (IM) and extramedullary (EM) tibial guides have been used to restore the desired extremity alignment. However, controversy exists regarding the superiority of either technique. We aimed to compare their functional outcomes and accuracy in providing neutral alignment after TKA. Methods: In a randomized, double-blinded clinical trial, we studied 98 patients undergoing primary TKA in two groups of IM and EM. We measured the medial proximal tibial angle (MPTA), varus angle (VA), and joint-line convergence angle with normal ranges of 90°±3°, 0-2°, and 0±3°, respectively, on a three-joint alignment view after three months. We also assessed functional outcomes at the last follow-up. Finally, we compared these outcomes between groups. Results: Eighty-four patients (IM=42, EM=42) were included in the final analysis (16 males, 68 females; mean age: 63.9±8.6 years; mean follow-up: 27±2.9 months). The mean postoperative alignment angles showed no significant difference, although MPTA outliers were significantly more frequent in the EM group (26.2% vs. 9.5% in IM, P=0.04). None of the functional outcomes showed a significant difference between groups. However, the mean ROM increase was significantly higher in VAs within ±3° of normal than those outside it (30.8 vs. 27.4, respectively; P=0.039). Conclusions: We conclude that both techniques were not different in terms of the mean alignment angles and functional outcomes. However, fewer MPTA outliers can be seen with IM. A postoperative mechanical axis within ±3° of neutral can result in a more ROM increase after one year. Trial registration: IRCT, IRCT20160809029286N5. Registered 21 April 2020, https://www.irct.ir/trial/46976