Background Making decision in alignment techniques in total knee arthroplasty (TKA) remains controversial. This study aims to identify the potential patients who were suitable for the kinematic (KA) or mechanical alignment (MA). Methods We reviewed 296 patients (296 TKAs, including 114 KA-TKAs and 182 MA-TKAs) who underwent unilateral TKA using a portable navigation system from 2016 to 2018 in our prospectively maintained database. The minimum followup was 1 year. Clinical outcomes including range of motion (ROM) and knee society score (KSS) were compared between KA-TKAs and MA-TKAs. Multiple regression models were used to evaluate the relationship between alignment techniques and KSS at the 1-year followup. Interaction and stratified analyses were conducted according to gender, age, body mass index (BMI), preoperative hip-knee-ankle (HKA) angle, ROM and KSS. Results ROM and KSS at the 1-year followup didn’t differ between MA-TKAs and KA-TKAs (all p>0.05). Alignment techniques did not associate with postoperative ROM (Adjusted β=0.4, 95% confidence interval [CI]: -0.3, 1.6; p=0.752) or 1-year KSS (Adjusted β=2.2, 95%CI: -0.7, 5.6; p=0.107). Patients with BMI more than 30 kg/m^2 achieved better 1-year KSS when using MA than KA (p for interaction<0.05), Additionally, patients with preoperative HKA angle more than 10 degrees varus benefited more from KA than MA (p for interaction<0.05). Conclusions Patients with severe varus deformity may be suitable for the KA technique, whereas MA should be used in obese patients.