Purpose Anterior cruciate ligament (ACL) injuries are often combined with lesions of the medial collateral ligament (MCL). The aim of this study was to evaluate treatment outcome of combined acute ACL and MCL lesions using functional US and clinical examination. Methods Patients aged > 18 years undergoing primary ACL reconstruction with concomitant operative (group 1) or non-operative treatment of the MCL (group 2) between 2014 and 2019 were included after a minimum follow-up of 12 months. Grade II MCL injuries with dislocated tibial or femoral avulsions and grade III MCL ruptures underwent ligament repair whereas grade II injuries without dislocated avulsions were treated non-operatively. Radiological outcome was assessed with functional US examinations. Medial knee joint width was determined in a supine position at 0° and 30° of knee flexion in unloaded and standardized loaded (= 15 Dekanewton) conditions using a fixation device. Clinical examination was performed and patient-reported outcomes were assessed by the use of the subjective knee form (IKDC), Lysholm score, and the Tegner activity scale. Results A total of 40 patients (20 per group) met inclusion criteria. Mean age of group 1 was 40 ± 12 years (60% female) with a mean follow-up of 33 ± 17 months. Group 2 showed a mean age of 33 ± 8 years (20% female) with a mean follow-up of 34 ± 15 months. Side-to-side differences in US examinations were 0.4 ± 1.5 mm (mm) in 0° and 0.4 ± 1.5 mm in 30° knee flexion in group 1, and 0.9 ± 1.1 mm in 0° and 0.5 ± 1.4 mm in 30° knee flexion in group 2, with no statistically significant differences between both groups. MCL repair resulted in lower Lysholm scores (75 ± 19 versus 86 ± 15; p < 0.05). No significant differences could be found for subjective IKDC or Tegner activity scores among the two groups. Conclusion A differentiated treatment concept in combined ACL and MCL injuries based on injury patterns leads to reliable postoperative ligamentous knee stability in US-based and clinical examinations. However, grade II and III MCL lesions with subsequent operative MCL repair (group 1) result in slightly poorer subjective outcome scores. Level of evidence Retrospective cohort study; Level III